JP2003201279A - Indole compound and its medicinal use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an indole compound or its medicinally permissible slat, having an HLGPa inhibitory activity and useful as a treating agent of diabetes mellitus. <P>SOLUTION: This indole compound expressed by general formula (1) [wherein, R<SP>1</SP>is H, a 1-6C alkyl or the like; R<SP>2</SP>is H or a halogen atom; R<SP>3</SP>is a 1-6C alkoxy, a halogen atom, nitro, amino, cyano, a 1-6C alkyl or the like; R<SP>4</SP>is H, a 1-6C alkyl or the like; R<SP>5</SP>is H, a 1-6C alkyl or the like; R<SP>6</SP>is H, a 1-6C alkyl or the like; and R<SP>7</SP>is expressed by formula (2) (wherein, R<SP>11</SP>to R<SP>15</SP>are each H, a 1-6C alkoxy, a halogen atom, nitro, cyano, a 1-6C aklyl or the like) or the like] and its medicinally permissible salt are provided. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to HLGPa (Hu
man Liver Glycogen Phospho
The present invention relates to a novel indole compound having lyase a) inhibitory activity and its pharmaceutical use. Furthermore, it relates to a therapeutic agent for diabetes which comprises a compound having an indole structure or a pharmaceutically acceptable salt thereof.

[0002]

BACKGROUND OF THE INVENTION Diabetes is a chronic disease caused by abnormal metabolism of sugars, lipids and amino acids due to insufficient insulin action. If untreated, it shows hyperglycemia and urinary glucose. Diabetes is divided into insulin-dependent and non-insulin-dependent, and about 90% of diabetic patients have non-insulin-dependent diabetes. Insulin-dependent diabetes mellitus
Since the insulin secretory capacity has disappeared, it is prone to ketonemia and acidosis, and if left unattended, diabetic coma occurs. There is no therapeutic effect on diet or oral hypoglycemic agents, and it can be treated only by insulin. On the other hand, in non-insulin-dependent diabetes mellitus (NIDDM), although the insulin action is lower than normal, ketonemia and acidosis tend to be poor and insulin is not always required for treatment.

As hypoglycemic agents currently used for the purpose of correcting hyperglycemia, insulin, sulfonylurea drugs (eg glibenclamide, tolbutamide), biguanide drugs (eg metformin), insulin sensitizers (eg , Troglitazone), and α-glucosidase inhibitors (eg, acarbose) have been used. An insulin preparation is a drug used for insulin-dependent diabetes mellitus, and surely lowers blood sugar, but it must be administered by injection and may cause hypoglycemia. Sulfonylurea agents stimulate pancreatic β cells and promote endogenous insulin secretion, but the timing and amount of insulin secretion are determined by the timing and dose of drug administration, regardless of blood glucose level. Therefore, as a side effect, hypoglycemia often occurs due to the continued action of the drug. In addition, digestive symptoms such as anorexia appear. Contraindicated in patients with severe ketosis or liver or renal dysfunction. Biguanide drugs do not stimulate pancreatic β-cells and do not cause hypoglycemia in both healthy subjects and diabetic patients when administered alone. The mechanism of action may be increased utilization of sugar by anaerobic glycolysis, suppression of gluconeogenesis, and suppression of intestinal absorption of sugar. As a side effect, it tends to cause relatively serious lactic acidosis. There is a thiazolidine derivative as a drug that improves insulin resistance, but the thiazolidine derivative compound does not exert an insulin secretagogue action, has an enhanced insulin action, and has an insulin receptor kinase activation action and a glucose uptake action in peripheral tissues. However, it is known that digestive symptoms, edema, etc. occur as side effects, and that red blood cell count, hematocrit, hemoglobin, and LDH increase as a side effect. [alpha] -Glucosidase inhibitors delay digestion and absorption of carbohydrates in the digestive tract to suppress postprandial blood glucose elevation, but side effects such as bloating, wheezing, and diarrhea pose a problem (for example, Non-Patent Documents). 1). As described above, the use of these drugs is limited because some side effects occur and there are patients who are ineffective, and a hypoglycemic drug having a new action mechanism has been desired.

In recent years, it has been known that in NIDDM patients, the amount of glucose released from the liver at the time of fasting is higher than that in healthy subjects. It is suggested that this sugar release from the liver may be a potential target for drug treatment against NIDDM. The sugar source for sugar release from the liver is glucose produced by gluconeogenesis and glycogenolysis. It was reported that in the diabetic patient, this glycogenolysis is largely involved in the release of sugar from the liver, and the rate of glycogenolysis during fasting was increased by 75% as compared with that of a healthy person. Further, it has been suggested that in NIDDM patients, glucose release from the liver transiently increases after glucose loading, and glycogenolysis is involved in this increase. Furthermore, it is also known that, in the sugar source disease type IV (liver glycogen phosphorylase deficiency), hypoglycemia is caused on an empty stomach.
These reports suggest that glycogenolysis plays an important role in glucose release from the liver.

On the other hand, this glycogenolysis is caused by HLGP.
It is known to produce glucose 1-phosphate (G1-P) and glycogen (n-1 glucose units) by superphosphate decomposing glycogen (n glucose units) catalyzed by a. ing. Therefore, the development of a novel therapeutic drug for diabetes having an HLGPa inhibitory action which is largely involved in glycogen decomposition has been advanced. However, the present situation is that nothing satisfying the active aspect has been found yet.

By the way, the following compounds are known as compounds having a structure similar to that of the present invention. For example, it is disclosed that the following compounds are useful as pest control agents.

[Chemical 19] The patent document does not disclose an indole compound as in the patent of the present application, and its use is completely different (see, for example, Patent Document 1).

Further, the following indole compounds similar in structure to the present invention are disclosed.

[Chemical 20] However, in this document, the indole compound as in the present application is HL
There is no disclosure that the compound has GPa inhibitory activity or that the compound is effective as a therapeutic drug for diabetes (see, for example, Non-Patent Document 2).

Further, the following indole compounds similar in structure to the present invention are disclosed.

[Chemical 21] However, in this document, the indole compound as in the present application is HL
There is no disclosure that the compound has GPa inhibitory activity or that the compound is effective as a therapeutic drug for diabetes (see, for example, Non-Patent Document 3).

On the other hand, the following general formula is disclosed as a compound having a glycogen phosphorylase inhibitory activity which is the same action as the present invention and having an indole structure.

[Chemical formula 22] (Here, R ₄ is a phenylalkyl group or the like, R ₅ is a hydrogen atom or the like, R ₆ is an alkoxycarbonyl group or the like, R ₂ is a hydrogen atom, R ₁ , R ₁₀ , and R ₁₁ are independently hydrogen atoms,
A halogen atom, etc., R ₃ is a hydrogen atom, etc., and A is —N =, etc.). Furthermore, the following compounds are disclosed as specific compounds.

[0010]

[Chemical formula 23] However, while the compound of our invention has a characteristic that it has an indole ring and hydrazine, and the hydrazine further bonds to the ring, the compound does not require a hydrazide skeleton (for example, Patent Document 1 2).

Currently, the development of a therapeutic drug for diabetes by inhibiting HLGPa is in progress, but its activity is still not satisfactory. Therefore, it has been strongly desired to develop an excellent HLGPa inhibitor which is more active and has no side effects as compared with the conventional therapeutic agents for diabetes.

[0012]

[Non-Patent Document 1] JOSLIN'S DIABETES MELLITUS 13Th Ed
iition 521-522

[Patent Document 1] Japanese Unexamined Patent Publication No. 5-39253

[Non-Patent Document 2] Tetrahedron Letter (Tetra
hedron Letter, (1972), 23
Volume, Pages 2333-2335

[Non-Patent Document 3] Yaoxue Xuebao (198
4), 19 (10), 737-741

[Patent Document 2] WO96 / 39384 (Patent Document 10-
(511687 publication)

[0013]

[Means for Solving the Problems] In view of the above problems, the present invention has conducted extensive studies to find a useful antidiabetic drug having HLGPa inhibitory activity. As a result, an indole compound represented by the following general formula (1) They found that they have a remarkable HLGPa inhibitory activity, and completed the present invention. More specifically, it is as shown in the following [1] to [20]. [1] General formula (1)

[Chemical formula 24] [In the formula, R ¹ is a hydrogen atom, a C _1-6 alkyl group or an acyl group; R ² is a hydrogen atom or a halogen atom; R ³ is a halogen atom, a C _1-6 alkyl group, C
_1-6 alkoxy group, nitro group, amino group, hydroxyl group, cyano group, acyl group, aralkyloxy group or thiazolyl group (the thiazolyl group may be substituted with a C _1-6 alkyl group or amino group) R ⁴ is a hydrogen atom or a C _1-6 alkyl group; R ⁵ is a hydrogen atom, C
_{A 1-6} alkyl group or a C _2-7 alkoxycarbonyl group; R ⁶ is a hydrogen atom, a C _1-6 alkyl group or an aralkyl group (the aralkyl group may be substituted with a halogen atom); R ⁷ is

[Chemical 25] {Where X is = O, = S or = NH; A is
-N ^(R 8) - ^{(wherein, R 8} is hydrogen _{atom, C 1-6} alkyl or optionally substituted aryl ^{group), - C (R 9)} (R 10) - (Where R ⁹ and R
¹⁰ are the same or different and are independently a hydrogen atom, a hydroxyl group, an amino group, a C _1-6 alkyl group, a C _1-6 hydroxyalkyl group, a C _2-7 alkoxycarbonylamino group or an acylamino group, or R ⁹ and R ¹⁰
_{May combine} with an adjacent carbon atom to form a C _3-7 cycloalkyl group), — (CH ₂ ) _m —NH—
(Where m is an integer of 1 to 4), -CO-, -S.
-Or a single bond; B is

[Chemical formula 26] (Wherein R ¹¹ , R ¹² , R ¹³ , R ¹⁴ or R ¹⁵
Are the same or different and independently have a hydrogen atom, a halogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group, a nitro group, a hydroxyl group, a cyano group, a haloalkyl group, an aralkyl group and a substituent. Optionally, an aryl group, an aryloxy group, a tetrazolyl group, a triazolyl group,-(CH
_{2) p} ^{-CO-R 19} (wherein, p is an integer of 0 or 1 to ^{4, R 19} is an optionally substituted aryl group, a hydroxyl _{group, C 1-6} alkoxy group or -N (R ²⁰ )
(R ²¹ )-(wherein R ²⁰ and R ²¹ are the same or different and are independently a hydrogen atom, a C _1-6 alkyl group,
An aralkyl group or a C _3-13 alkoxycarbonylalkyl group, or R ²⁰ and R ²¹ together with the adjacent nitrogen atom,

[Chemical 27] (Here, q is an integer of 1 to 3, and R²²Is hydrogen
Child, hydroxyl group, C_1-6Alkoxy group, amino group, C
_2-12Dialkylamino group or C_2-7Alkoxyca
May be a carbonyl group).
), -O- (CH_Two)_r-R²³(Where r is 1 to
R is an integer of 4²³Is hydroxyl group, amino group, C_{2- 7}
Alkylcarbonyloxy group or -CO-R²⁴(here
And R²⁴Is a hydroxyl group, C_1-6Alkoxy group or -N
(R²⁵) (R²⁶)-(Where R²⁵And R
²⁶Are the same or different and are a hydrogen atom, C_1-6Archi
R or aralkyl, or R²⁵And R
²⁶Together with the adjacent nitrogen atom,

[Chemical 28] (Where q'and R^{22 '}Are q and R respectively²²When
Synonyms) may be formed))),-
O-CO-R²⁷(Where R²⁷Is C_1-6Alkyl
Amino group or C_2-12A dialkylamino group),
Or -N (R²⁸) (R²⁹) (Where R²⁸And R
²⁹Are the same or different and are a hydrogen atom, C _1-6Archi
Group, aryl group which may have a substituent, acyl
Group,-(CH _Two)_{p '}-COO-R^Thirty(Where p ’
Is synonymous with p and R^ThirtyHas a hydrogen atom and a substituent
Optionally an aryl group or C_1-6Alkyl group (the C
_1-6The alkyl group is a hydroxyl group, a trifluoromethyl group,
An optionally substituted aryl group, morpholino group or
Is optionally substituted with a carboxyl group), -C
ON (R³¹) (R³²) (Where R³¹And R³²
Are the same or different and are a hydrogen atom, C_1-6Alkyl group
Or an aryl group which may have a substituent),
CO-R³³(Where R³³Is C_1-6Alkyl group
Is an aryl group which may have a substituent), -C
O- (CH_Two)_{r '}-R³⁴(Where r'is synonymous with r
And R³⁴Is C_1-6Alkylamino group, C
_2-12Dialkylamino group, C_1-6Alkoxy group
Is C_2-7Is an alkylcarbonyloxy group)
R) and R^16b~ R¹⁶ⁿAnd R^17b~ R
¹⁷ⁿAre the same or different and are a hydrogen atom, a halogen atom,
C_1-6Alkyl group, amino group, hydroxyl group, C_1-6Al
Coxy group or -CON (R^{31 '}) (R^{32 '})(here
And R^{31 '}And R^{32 '}Is R³¹And R³²Synonymous with
Yes, and R¹⁸Is a hydrogen atom or C_2-7Arcoki
Is a carbonyl group, and Y is -S-, -O- or -N.
(R³⁵)-(Where R³⁵Is a hydrogen atom or C_{1 -6}
Is an alkyl group), and n is 0 or an integer of 1 to 4.
Is)} or R⁶And R⁷Adjacent to
Together with the nitrogen atom

[Chemical 29] {Where R³⁶And R³⁷Are the same or different,
Elementary atom, halogen atom, C_1-6Alkyl group, C_1-6
Alkoxy group, amino group, nitro group, hydroxyl group, C _2-7
Alkoxycarbonyl group, carboxyl group, C_2-7Ha
Roalkylcarbonylamino group or -O-CO-R⁴¹
(Where R⁴¹Is C_1-6Alkyl group, C_1-6A
Rukylamino group or C_2-12Is a dialkylamino group
Z) is -CH_Two-CH_Two-, -C
(R⁴²) = CH-, -C (R^{42 '}) = N−, −N =
N-, -CO-, -CO-O-, -CO-CH_Two-O
-, -CH_Two-CO-NH-, -C (R^{42 ''}) (R
⁴³) -N (R⁴⁴)-(Where R⁴², R^{42 '},
R^{42 ''}And R⁴³Are the same or different hydrogen atoms,
C_1-6Ali which may have an alkyl group or a substituent
Group, and R⁴⁴Is a hydrogen atom, C_1-6Alkyl
Group (the C_1-6The alkyl group is a carboxyl group or C
_2-7(May be substituted with an alkoxycarbonyl group)
Is C_2-7An alkoxycarbonyl group) or -C
(U) -N (R^{44 '})-(Where U is = O or = S
And R^{44 '}Is R⁴⁴(Synonymous with)
And each group is a group adjacent to the nitrogen atom on the fused ring of formula (i).
Children are listed on the left edge); R³⁸Is a hydrogen atom, a substituent
An aryl group or a heteroaryl group which may have
R; R³⁹And R⁴⁰Are the same or different and
Child, C_1-6Alkyl group, C_{1 -6}Alkoxy group or C
_2-7An alkoxycarbonyl group or R^Three
9And R⁴⁰Together with the adjacent carbon atom,

[Chemical 30] W may be formed; W is -CO-, -CS- or -CH
₂ -; _{V 1} is -CO -, - CS- or -CH ₂ -
V ₂ is —O—, —CH ₂ — or —N (R ⁴⁵ ).
-(Wherein R ⁴⁵ is a hydrogen atom, a C _1-6 alkyl group or an aryl group which may have a substituent); and V ₃ is -CH (R ⁴⁶ )-or -N ( R ^{46 '} )-
(Wherein R ⁴⁶ and R ^{4 6 ′} are each a hydrogen atom, an aralkyl group, a heteroaryl group or an aryl group which may have a substituent). Indole compound, pharmaceutically acceptable salt or prodrug thereof. [2] R ⁶ is a hydrogen atom, a C _1-6 alkyl group or an aralkyl group (the aralkyl group may be substituted with a halogen atom); and R ⁷ is

[Chemical 31] {Where X is = O, = S or = NH; A is
—N (R ^{8 ′} ) — (wherein R ^{8 ′} is a hydrogen atom, C
_1-6 alkyl group or a phenyl group which may have a substituent), -C (R9 ^' ) (R10 ^' )-(wherein R9 ^' and R10 ^' are the same or different) , Hydrogen atom, hydroxyl group, amino group, C _1-6 alkyl group, C _1-6
A hydroxyalkyl group, a C _2-7 alkoxycarbonylamino group or an acylamino group, or R ^{9 ′}
And R ^{10 ′} together with the adjacent carbon atom, C
_3-7 cycloalkyl group may be formed),-(CH
₂ ) _m- NH- (where m is an integer of 1 to 4),
-CO-, -S- or a single bond; B is

[Chemical 32] ^{(Wherein, R 11 ', R 12'} , R 13 ', R 14' or ^{R 15 'are} the same or different, a hydrogen atom, a halogen _{atom, C 1-6 alkyl, C 1-6} alkoxy group, Nitro group, hydroxyl group, cyano group, haloalkyl group, aralkyl group, optionally substituted phenyl group, aryloxy group, tetrazolyl group, triazolyl group,-(CH
₂ ) _p- CO-R19 ^' (here, p is 0 or an integer of 1 to 4, R19 ^' is a phenyl group which may have a substituent, a hydroxyl group, a _C1-6 alkoxy group or -N (R
^{20) (R 21)} - ^{(wherein, R 20} and ^{R 21} are the same meaning as claim _{1)), - O- (CH} 2) r -R
²³ (wherein r and R ²³ are as defined in claim 1), —O—CO—R ²⁷ (wherein R ²⁷ is in claim 1).
Synonymous with), or -N (R < ^{28 '} >) (R <^29'> ).
(Here, R ^{28 ′} and R ^{29 ′} are the same or different and each is a hydrogen atom, a C _1-6 alkyl group, an optionally substituted phenyl group, an acyl group, or — (CH ₂ ) _{p ′.} -C
OO-R ^{30 '} (wherein p'has the same meaning as in claim 1, R ^30' represents a hydrogen atom, a phenyl group which may have a substituent or a C _1-6 alkyl group (the C _{1- 6} alkyl group is a hydroxyl group, a trifluoromethyl group, a phenyl group which may have a substituent, a morpholino group or a carboxyl group may be substituted), and -CON (R
^{31 ″} ) (R ^{32 ″} ) (where R ^{31 ″} and R
^{32 ″} are the same or different and each is a hydrogen atom, a C _1-6 alkyl group or a phenyl group which may have a substituent), —CO—R ^{33 ′} (wherein R ^{33 ′} is C _1-6
A phenyl group which may have an alkyl group or a substituted _{group), - CO- (CH 2)} r '-R 34 ( where
r ′ and R ³⁴ are as defined in claim 1) and R ^{16b ′ to} R ^{16n ′} and R ^{17b ′ to} R.
^{17n ′} are the same or different and each represents a hydrogen atom, a halogen atom, a C _1-6 alkyl group, an amino group, a hydroxyl group, C _1-6.
Alkoxy group or -CON (R ^{31 '''} ) (R
^{32 ′ ″} ) (wherein R ^{31 ′ ″} and R ^{32 ′ ″)}
Is synonymous with R ^{31 ″} and R ^{32 ″} ), and R
¹⁸ , Y and n are as defined in claim 1), or R ^{6 ′} and R ^{7 ′} together with the adjacent nitrogen atom

[Chemical 33] {Wherein R ³⁶ and R ³⁷ are as defined in claim 1;
Z ′ is —CH ₂ —CH ₂ —, —C (R ⁴² ) ═CH
-, -C ( ^{R42 '} ) = N-, -N = N-, -CO-,
_{-CO-O -, - CO-} CH 2 -O -, - CH 2 -CO
-NH-, -C (R42 ^'' ) ( ^R43 ) -N
^{(R 44)} - ^{(wherein, R 4 2, R 42 '} , R 42''
And R ⁴³ is the same or different and is a hydrogen atom, a C _1-6 alkyl group or a phenyl group which may have a substituent, and R ⁴⁴ has the same meaning as in claim 1) or —C (U) —. N
( ^{R44 '} )-(wherein U and ^R44' are defined in Claim 1
R ^{38 ′} is a hydrogen atom , a phenyl group which may be substituted with a halogen atom or a C _1-6 alkyl group, or a pyridyl group; R ^{39 ′} and R ^{40 ′} are both hydrogen. An atom or R ^{39 '}
And R ^{40 '} , together with the adjacent carbon atom,

[Chemical 34] May be formed; W and V₁Is synonymous with claim 1.
R; V_Two'Is -O-, -CH_Two-Or-N (R⁴⁵) −
(Where R⁴⁵Is a hydrogen atom, C_1-6An alkyl group,
A phenyl group which may be substituted with a halogen atom
It is; V_Three'Is -CH (R⁴⁶)-Or -N (R
^{46 '})-(Where R⁴⁶And R ^{46 '}Is that
Hydrogen atom, benzyl group, thienyl group, or halogen atom
Child, hydroxy group or C_1-6Substitute with an alkoxy group
Is a phenyl group which may be
May be used] [1] described indole compound,
A pharmaceutically acceptable salt or prodrug thereof. [3] R⁶Is a hydrogen atom, C_1-6Alkyl group or
Aralkyl group (the aralkyl group is substituted with a halogen atom)
R); R⁷But,

[Chemical 35] {Where X is as defined in claim 1; A is -N (R
^{8 ″} )-(wherein R ^{8 ″} is a hydrogen atom, a C _1-6 alkyl group or an aryl group which may have a substituent), —C (R ^{9 ″} ) (R ^{10 ′ '} )-(Where R
^{9 ″} and R ^{10 ″} are the same or different and each is a hydrogen atom,
A hydroxyl group, an amino group, a C _1-6 alkyl group, a C _1-6 hydroxyalkyl group or a C _2-7 alkoxycarbonylamino group, or R ^{9 ″} and R ^{10 ″} together with adjacent carbon atoms turned to _may form a _{C 3-7} cycloalkyl _{group), - (CH 2) m} -NH- ( wherein, m is as defined in claim 1), - CO- or a single bond ; B is

[Chemical 36] (Where R ^{11 ″} , R ^{12 ″} , R ^{13 ″} , R
^{14 ″} or R ^{15 ″} are the same or different and each is a hydrogen atom, a halogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group, a nitro group, a hydroxyl group, a cyano group, a haloalkyl group, an aralkyl group or a substituent. aryl group which may have a group, an aryloxy group, a tetrazolyl group, a triazolyl _{group, - (CH 2) p -CO} -R 19 ( wherein, p and ^{R 19} are as defined in claim 1), -O- _{(CH 2) r}
-R ²³ (where, r and ^{R 23} are as defined in claim ^{1), - O-CO-} R 27 ( ^{wherein, R 27} is as defined in claim 1) or -N ^{(R 28 ''} )
(R ^{29 ″} ) (wherein R ^{28 ″} and R
^{29 ″} are the same or different and each is a hydrogen atom, a C _1-6 alkyl group, an aryl group which may have a substituent,
_{(CH 2) p '-COO-} R 30''( wherein, p' is synonymous with p, ^{R 30 ''} is a hydrogen atom or a _{C 1-6} alkyl group (the _{C 1-6} alkyl group, It may be substituted with a hydroxyl group, a trifluoromethyl group or a carboxyl group)
, -CON (R ³¹ ) (R ³² ) (wherein R
³¹ and R ³² have the same meaning as in claim 1), —CO—R
³³ (wherein R ³³ is as defined in claim 1), -C
_{O- (CH 2) r '-R} 34 ( where, r' and R
³⁴ is the same as in claim 1)), and R
^16b to R ¹⁶ⁿ and ^R 17b ^{to R 17n} has the same meaning as defined in claim ^{1, R 18} has the same meaning as defined in claim 1, Y '' is -S- or -N ^{(R 35)} - ^(wherein, R ³⁵ is synonymous with claim 1, and n is synonymous with claim 1.}
Or R ⁶ and R ⁷ together with the adjacent nitrogen atom

[Chemical 37] {Where R^{36 ''}And R^{37 ''}Are the same or different
, Hydrogen atom, halogen atom, C_1-6An alkyl group,
C_1-6Alkoxy group, amino group, hydroxyl group or -OC
OR⁴¹(Where R⁴¹Is synonymous with claim 1.)
Z ″ is —CH_Two-CH_Two-, -C
(R⁴²) = CH-, -N = N-, -CO-, -CO-
O-, -CO-CH_Two-O-, -CH_Two-CO-NH
-, -C (R ^{42 ''}) (R⁴³) -N (R^{44 ''})
-(Where R⁴², R^{42 ''}And R⁴³Is claim 1
Is synonymous with R^{44 ''}Is a hydrogen atom, C_1-6Al
Kill group or C_2-7It is an alkoxycarbonyl group)
Is -C (U) -N (R^{44 '' '})-(Where U is =
O or = S, R^{44 '''}Is R^{44 ''}Synonymous with
Yes) Yes; R^{38 ''}Has a hydrogen atom or a substituent
An optionally substituted aryl group; R^{39 ''}And R
^{40 ''}Are the same or different and are a hydrogen atom, C_1-6A
Rukiru group or C_2-7Is an alkoxycarbonyl group
Or R^{39 ''}And R^{40 ''}Adjacent to carbon
Being with a child,

[Chemical 38] W ″ is —CO— or —CH ₂ —; V ₁ and V ₂ are as defined in claim 1; V ₃ is —CH (R ^{46 ″} ) — or — N (R ^{46 '''} )-
(Wherein R ^{46 ′ ′} and R ^{46 ′ ″} are the same or different and each is a hydrogen atom or an aryl group which may have a substituent)}. [1] The indole compound according to [1], a pharmaceutically acceptable salt or prodrug thereof. [4] The indole compound according to [1] to [3], wherein R ¹ , R ² , R ⁴ , R ⁵ and R ⁶ are hydrogen atoms, or a pharmaceutically acceptable salt or prodrug thereof. [5] The indole compound according to [4], wherein R ³ is a halogen atom or a C _1-6 alkyl group, a pharmaceutically acceptable salt or prodrug thereof. [6] X is ═O, A is a single bond, and B is

[Chemical Formula 39] [5] The indole compound according to [5], a pharmaceutically acceptable salt or prodrug thereof. [7] X is = NH, A is a single bond, and B
But

[Chemical 40] [4] The indole compound according to [4], a pharmaceutically acceptable salt or prodrug thereof. [8] R ⁶ and R ⁷ together with the adjacent nitrogen atom

[Chemical 41] An indole compound according to [1] to [3], which forms
A pharmaceutically acceptable salt or prodrug thereof. [9] Benzoic acid 2- (5-chloro-1H-indole
2-L-carbonyl) hydrazide, 2-aminobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-hydroxybenzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
De, 3- (2- (2- (5-chloro-1H-indole
-2-Carbonyl) hydrazinocarbonyl) phenylca
Luvamoyloxy) -2,2-dimethylpropionic acid,
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) -1-methylhydrazide, benzoic acid 2-
(1-Acetyl-5-chloro-1H-indole-2-
Carbonyl) hydrazide, 5-chloro-1H-indole
2-Carboxylic acid 2- (imino-phenyl-methyl)
) Hydrazide, 5-aminothiazole-4-carvone
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, benzoic acid 2- (5-fluoro-1)
H-indole-2-carbonyl) hydrazide, cyclo
Hexanecarboxylic acid 2- (5-fluoro-1H-yne
Dole-2-carbonyl) hydrazide, thiophene-2
-Carboxylic acid 2- (5-fluoro-1H-indole
-2-Carbonyl) hydrazide, 4-nitrobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-methylbenzoic acid 2- (5-chloro)
-1H-indole-2-carbonyl) hydrazide,
4-Methylbenzoic acid 2- (5-chloro-1H-indo
2-carbonyl) hydrazide, 2-methoxybenzo
Aromatic acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 3-methoxybenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 4-methoxybenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 3-methyi
Le benzoic acid 2- (5-chloro-1H-indole-2
-Carbonyl) hydrazide, 2-chlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-chlorobenzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 4-ku
Lolobenzoic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 4- (2- (5-chloro
-1H-indole-2-carbonyl) hydrazinocar
Bonyl) benzoic acid methyl ester, cyclohexanecal
Boronic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 2,4-dichlorobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2,6-dichlorobenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
De, 2,4-difluorobenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, bif
Phenyl-2-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, 3-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 4-fluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-trifluoromethylbenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 4-trifluoromethylbenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
De, 2-trifluoromethylbenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
Benzoic acid 2- (5-methyl-1H-indole-2-
Carbonyl) hydrazide, benzoic acid 2- (5-chloro)
-3-Methyl-1H-indole-2-carbonyl) hi
Dolazide, benzoic acid 2- (5,7-dichloro-1H-
Indole-2-carbonyl) hydrazide, 2-amino
Benzoic acid 2- (5-isopropyl-1H-indole)
-2-Carbonyl) hydrazide, 2-amino-4-fur
Orobenzoic acid 2- (5-isopropyl-1H-indo)
2-carbonyl) hydrazide, 2-aminobenzoic acid
Acid 2- (5-Fluoro-1H-indole-2-cal
Bonyl) hydrazide, 2-aminobenzoic acid 2- (6-
Chloro-1H-indole-2-carbonyl) hydrazide
3-amino-4- (2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazinocarbonyl) rest
Aromatic acid methyl ester, 3-aminoisonicotinic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, isonicotinic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide, nicotinic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, pyridine-2-carboxylic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 3- (dimethylamino) benzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
N- (3- (2- (5-chloro-1H-indole
-2-carbonyl) hydrazinocarbonyl) phenyl)
Acetamide, N- (2- (2- (5-chloro-1H-
Indole-2-carbonyl) hydrazinocarbonyl)
Phenyl) acetamide, 4-fluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl)-
2-methylhydrazide, 2- (2- (2- (5-chloro
-1H-indole-2-carbonyl) hydrazinocar
Bonyl) phenoxy) acetic acid methyl ester, 2- (2
-(2- (5-chloro-1H-indole-2-carb
Nil) hydrazinocarbonyl) phenoxy) acetic acid, 2
-(Dimethylamino) benzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 2-
(2- (5-chloro-1H-indole-2-carboni
Le) hydrazinocarbonyl) phenoxy-N, N-dime
Cylacetamide, 2-methylaminobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2-amino-4-chlorobenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 2-amino-6-chlorobenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
2-amino-3-chlorobenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
2-Amino-5-chlorobenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 4-
Cyanobenzoic acid 2- (5-chloro-1H-indole
-2-carbonyl) hydrazide, 4- (1H-tetrazo
Rol-5-yl) benzoic acid 2- (5-chloro-1H-)
Indole-2-carbonyl) hydrazide, 3- (1H
-Tetrazol-5-yl) benzoic acid 2- (5-chloro)
-1H-indole-2-carbonyl) hydrazide,
2- (2- (2- (5-chloro-1H-indole-2
-Carbonyl) hydrazinocarbonyl) anilino) vinegar
Acid, 2-aminobenzoic acid 2- (5-methyl-1H-i)
Ndole-2-carbonyl) hydrazide, 2-amino-
4-Fluorobenzoic acid 2- (5-methyl-1H-yne
Dole-2-carbonyl) hydrazide, methyl 2-
(2- (5-methyl-1H-indole-2-carbonyl
Le) hydrazinocarbonyl) phenyl) carbamate,
2- (2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazinocarbonyl) phenyl dimethyl carbonate
Lubamate, 2-aminobenzoic acid 2- (5-ethyl-
1H-indole-2-carbonyl) hydrazide, 2-
Amino-4,5-difluorobenzoic acid 2- (5-methyl
Ru-1H-indole-2-carbonyl) hydrazide,
2- (2-hydroxyethoxy) benzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
2- (3- (2- (5-chloro-1H-indole
-2-Carbonyl) hydrazinocarbonyl) phenoki
Si) acetic acid methyl ester, 2- (3- (2- (5-chloro
B-1H-indole-2-carbonyl) hydrazinoca
Lubonyl) phenoxy) acetic acid, 2- (3- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) phenoxy) -N, N-dimethylacetate
Amide, N- (1,2,3,4-tetrahydro-7-di
Toro-2,4-dioxoquinazolin-3-yl) -5-
Chloro-1H-indole-2-carboxylic acid amide, 2
-Methylthiazole-4-carboxylic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
4- (2H- [1,2,4] triazol-3-yl) an
Benzoic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 3- (2H- [1,2,4] tri
Azol-3-yl) benzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 1,3
-Dihydroxy-2-propyl (2- (2- (5-
Lolo-1H-indole-2-carbonyl) hydrazino
Carbonyl) phenyl) carbamate, 3-((2-
(2- (5-chloro-1H-indole-2-carboni
Le) hydrazinocarbonyl) phenyl) carbamoylo
Xy) -2,2-dimethylpropionic acid, thiophene-
2-carboxylic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide, furan-2-carvone
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 2,6-dichloronicotinic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 1H-pyrrole-2-carboxylic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 1H-imidazole-4-carboxylic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, pyrazine-2-carboxylic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, thio
Phen-3-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, furan-3-
Carboxylic acid 2- (5-chloro-1H-indole-2
-Carbonyl) hydrazide, 5-chlorothiophene-2
-Carboxylic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 3-chlorothiophene-
2-carboxylic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide, 1-methyl-1H-pi
Roll-2-carboxylic acid 2- (5-chloro-1H-i)
Ndol-2-carbonyl) hydrazide, 5-methylthio
Offene-2-carboxylic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide, 3-methyl
Thiophene-2-carboxylic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 2,6-
Difluorobenzoic acid 2- (5-chloro-1H-indo
2-carbonyl) hydrazide, 2,3-difluor
B-benzoic acid 2- (5-chloro-1H-indole-2)
-Carbonyl) hydrazide, 5-chloro-1H-indo
2-carboxylic acid 2- (naphthalene-1-carbohydrate)
Nyl) hydrazide, 3,4,5-trifluorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2,3,4,5-tetrafluorobenzoate
Aromatic acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 2-amino-4-methylbenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-amino-4-fluorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-amino-5-methylbenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-amino-6-methylbenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2-amino-3-methylbenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 2-amino-4,5-difluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-aminothiophene-2-carboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-aminobenzoic acid 2- (5-bromo-
1H-indole-2-carbonyl) hydrazide, 2-
Amino-4-fluorobenzoic acid 2- (5-bromo-1
H-indole-2-carbonyl) hydrazide, 1H-
Pyrazole-4-carboxylic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, methyl
(2- (2- (5-fluoro-1H-indole-2-
Carbonyl) hydrazinocarbonyl) phenyl) carba
Mate, 1-methyl-1H-pyrrole-2-carboxylic acid
2- (5-methyl-1H-indole-2-carboni
Le) hydrazide, thiophene-3-carboxylic acid 2-
(5-methyl-1H-indole-2-carbonyl) hi
Dorazide, 4H-thieno [3,2-b] pyrrole-5-
Carboxylic acid 2- (5-chloro-1H-indole-2
-Carbonyl) hydrazide, phenyl (2- (2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazinocarbonyl) phenyl) carbamate, benzi
Ru (2- (2- (5-chloro-1H-indole-2
-Carbonyl) hydrazinocarbonyl) phenyl) calc
Bamate, 2-hydroxyethyl (2- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) phenyl) carbamate, 3-hydroxy
Cypropyl (2- (2- (5-chloro-1H-indo
2-carbonyl) hydrazinocarbonyl) pheny
Carbamate, 2-((2- (5-chloro-1H-
Indole-2-carbonyl) hydrazinocarbonyl)
Phenyl) carbamoyloxy) acetic acid, 2-((2-
(2- (5-chloro-1H-indole-2-carboni
Le) hydrazinocarbonyl) phenyl) carbamoylo
Xymethyl) -2-methylmalonic acid, methyl 2- (2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazinocarbonyl) phenyl carbamate, cyclo
Hexanecarboxylic acid 2- (5-chloro-1H-indo)
2-carbonyl) -1-methylhydrazide, thio
Phen-2-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) -1-methylhydrazide,
Benzoic acid 2- (1H-indole-2-carbonyl)
Hydrazide, benzoic acid 2- (5-chloro-1-methyl)
-1H-indole-2-carbonyl) hydrazide, cheap
Benzoic acid 2- (5-methoxy-1H-indole-2-
Carbonyl) hydrazide, benzoic acid 2- (5-isop
Ropyr-1H-indole-2-carbonyl) hydrazide
De, benzoic acid 2- (5-nitro-1H-indole-
2-carbonyl) hydrazide, benzoic acid 2- (5-
Benzyloxy-1H-indole-2-carbonyl) hi
Dolazide, benzoic acid 2- (6-chloro-1H-india
2-carbonyl) hydrazide, 6H-thieno
[2,3-b] Pyrrole-5-carboxylic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((2-Fluorophenyl) -imino-methyl) hi
Dorazide, 5-chloro-1H-indole-2-carb
Acid 2-((3-fluorophenyl) -imino-methyl
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2-((4-fluorophenyl) -imino
-Methyl) hydrazide, 5-chloro-1H-indole
2-carboxylic acid 2- (imino- (p-tolyl) -me
Chill) hydrazide, 5-chloro-1H-indole-2
-Carboxylic acid 2-((4-chlorophenyl) -imino
-Methyl) hydrazide, 5-chloro-1H-indole
-2-carboxylic acid 2-((3-chlorophenyl) -i
Mino-methyl) hydrazide, 5-chloro-1H-indo
-2-carboxylic acid 2-((2-chlorophenyl)
-Imino-methyl) hydrazide, 5-chloro-1H-i
Ndole-2-carboxylic acid 2- (imino- (o-tri
) -Methyl) hydrazide, 5-chloro-1H-indo
2-carboxylic acid 2- (imino- (m-tolyl)
-Methyl) hydrazide, 5-chloro-1H-indole
2-carboxylic acid 2- (imino- (thiophene-2-
Yl) -methyl) hydrazide, 5-chloro-1H-yne
Dole-2-carboxylic acid 2- (imino- (pyridine-
2-yl) -methyl) hydrazide, 5-chloro-1H-
Indole-2-carboxylic acid 2-((furan-2-i
) -Imino-methyl) hydrazide, 5-chloro-1H
-Indole-2-carboxylic acid 2-((2-chloro-
6-Fluorophenyl) -imino-methyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (2-trifluoromethylphenyl)-
Methyl) hydrazide, 5-chloro-1H-indole-
2-carboxylic acid 2- (imino- (pyrazin-2-i
) -Methyl) hydrazide, 3-aminobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-methoxybenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 5-
Amino-2-methylthiazole-4-carboxylic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 5-chloro-1H-indole-2-carb
Acid (1,2,3,4-tetrahydro-2,4-dio
Xoxoquinazolin-3-yl) amide, 5-chloro-1H
-Indole-2-carboxylic acid (2,3-dihydro-
2,4-dioxo-4H-benzo [e] [1,3] oxy
Sazin-3-yl) amide, 5-chloro-1H-indo
-2-carboxylic acid (1,2,3,4-tetrahydr
Lo-4-oxo-2-thioxoquinazolin-3-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (3,4-dihydro-2-methyl-4-oxoquina
Zolin-3-yl) amide, 5-chloro-1H-indo
-2-carboxylic acid (3,4-dihydro-4-oxy
Soquinazolin-3-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid (1,2,3,4-tet
Lahydro-4-oxoquinazolin-3-yl) amide,
5-chloro-1H-indole-2-carboxylic acid
(1,2,3,4-tetrahydro-2,5-dioxo-
5H-benzo [e] [1,4] diazepin-4-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (2,3,4,5-tetrahydro-3,5-dioxy
So-benzo [f] [1,4] oxazepin-4-y
Ru) amide, 5-isopropyl-1H-indole-2
-Carboxylic acid (1,2,3,4-tetrahydro-2,
4-dioxoquinazolin-3-yl) amide, 5-iso
Propyl-1H-indole-2-carboxylic acid (7-
Fluoro-1,2,3,4-tetrahydro-2,4-di
Oxoquinazolin-3-yl) amide, 5-fluoro-
1H-indole-2-carboxylic acid (1,2,3,4
-Tetrahydro-2,4-dioxoquinazolin-3-i
) Amide, 6-chloro-1H-indole-2-cal
Boronic acid (1,2,3,4-tetrahydro-2,4-di
Oxoquinazolin-3-yl) amide, 3-((5-qua
Lolo-1H-indole-2-carbonyl) amino)-
1,2,3,4-tetrahydro-2,4-dioxoquina
Zoline-7-carboxylic acid methyl ester, 3-((5-
Chloro-1H-indole-2-carbonyl) amino)
-1,2,3,4-tetrahydro-2,4-dioxoki
Nazolin-7-carboxylic acid, 5-chloro-1H-indo
-2-carboxylic acid (1,2,3,4-tetrahydr
B-2,4-dioxo-6- (trifluoroacetyl
Mino) quinazolin-3-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid (6-amino-1,
2,3,4-tetrahydro-2,4-dioxoquinazoli
N-3-yl) amide, 5-chloro-1H-indole
-2-carboxylic acid (5-chloro-1,2,3,4-tetracarboxylic acid
Trahydro-2,4-dioxoquinazolin-3-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (6-chloro-1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-3-yl) amide, 5-
Chloro-1H-indole-2-carboxylic acid (7-
Lolo-1,2,3,4-tetrahydro-2,4-dioki
Soquinazolin-3-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid (8-chloro-1,2,
3,4-tetrahydro-2,4-dioxoquinazoline-
3-yl) amide, 2- (3-((5-chloro-1H-
Indole-2-carbonyl) amino) -1,2,3
4-Tetrahydro-2,4-dioxoquinazoline-1-
-Yl) acetic acid, 2- (3-((5-chloro-1H-indo
-2-carbonyl) amino) -1,2,3,4-thel
Trahydro-2,4-dioxoquinazolin-1-yl)
Acetic acid methyl ester, 5-methyl-1H-indole-
2-carboxylic acid (1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-3-yl) amide, 5-
Methyl-1H-indole-2-carboxylic acid (7-f
Luoro-1,2,3,4-tetrahydro-2,4-dio
Xoxoquinazolin-3-yl) amide, 5-ethyl-1H
-Indole-2-carboxylic acid (1,2,3,4-tetracarboxylic acid
Trahydro-2,4-dioxoquinazolin-3-yl)
Amide, 5-methyl-1H-indole-2-carvone
Acid (6,7-difluoro-1,2,3,4-tetrahi
Doro-2,4-dioxoquinazolin-3-yl) ami
5-methyl-1H-indole-2-carboxylic acid
(1,2,3,4-tetrahydro-6-methoxy-2,
4-dioxoquinazolin-3-yl) amide, 5-methyi
Ru-1H-indole-2-carboxylic acid (1,2,
3,4-tetrahydro-6-hydroxy-2,4-dio
Xoxoquinazolin-3-yl) amide, acetic acid 3-((5
-Methyl-1H-indole-2-carbonyl) ami
No) -1,2,3,4-tetrahydro-2,4-dioki
Soquinazolin-6-yl ester, 5-chloro-1H-
Indole-2-carboxylic acid (1,2,3,4-tet
Lahydro-2,4-dioxo-1-propylquinazoline
-3-yl) amide, 5-chloro-1H-indole-
2-carboxylic acid (1,2,3,4-tetrahydro-1
-Methyl-2,4-dioxoquinazolin-3-yl) a
Mido, 5-chloro-1H-indole-2-carboxylic acid
(2,4-dioxoperhydropyrimidin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (4-oxo-2-thioxoperhydropyrimy
Zin-3-yl) amide, 5-chloro-1H-indole
2-carboxylic acid (2,4-dioxo-1-phenyl
Luperhydropyrimidin-3-yl) amide, 5-chloro
B-1H-indole-2-carboxylic acid (4-oxo
-1-Phenylperhydropyrimidin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(1- (4-fluorophenyl) -2,4-dioxopa
-Hydropyrimidin-3-yl) amide, 5-chloro-
1H-indole-2-carboxylic acid (2,4-dioxy
So-1- (pyridin-2-yl) perhydropyrimidine
-3-yl) amide, 5-chloro-1H-indole-
2-carboxylic acid (1- (3-fluorophenyl)-
2,4-dioxoperhydropyrimidin-3-yl) a
Mido, 5-chloro-1H-indole-2-carboxylic acid
(1- (2-fluorophenyl) -2,4-dioxo
Perhydropyrimidin-3-yl) amide, 5-fluor
B-1H-indole-2-carboxylic acid (2,4-di
Oxo-1-phenyl-perhydropyrimidin-3-i
) Amide, 5-methyl-1H-indole-2-cal
Boronic acid (2,4-dioxo-1-phenyl-peroxide
Lopyrimidin-3-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid (1- (3-chlorophene
Nil) -2,4-dioxoperhydropyrimidine-3-
Yl) amide, 5-chloro-1H-indole-2-ca
Rubonic acid (2,4-dioxo-1- (m-tolyl) pa
-Hydropyrimidin-3-yl) amide, 5-chloro-
1H-indole-2-carboxylic acid (2,4-dioxy
So-1- (p-tolyl) perhydropyrimidin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (1- (4-chlorophenyl) -2,4-dio
Xoxoperhydropyrimidin-3-yl) amide, 5-qua
Lolo-1H-indole-2-carboxylic acid (2,4-
Dioxo-1- (o-tolyl) perhydropyrimidine-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid ((4S) -2,5-dioxo-4-phenyl)
Phenylimidazolidin-1-yl) amide, 5-chloro
-1H-indole-2-carboxylic acid (2,4-dio
Xo-1-phenylimidazolidin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(4-oxo-1-phenyl-2-thioxoimidazole
Zin-3-yl) amide, 5-chloro-1H-indole
2-carboxylic acid (4-oxo-1-phenylimi
Dazolidin-3-yl) amide, 5-chloro-1H-i
Ndole-2-carboxylic acid (2-oxo-1-phenyl
Rumidazolidin-3-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid ((4R) -2,5
-Dioxo-4-phenylimidazolidin-1-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid ((4S) -1,3-dioxo-perhydropyrrolo
[1,2-c] imidazol-2-yl) amide, 5-
Chloro-1H-indole-2-carboxylic acid ((4
R) -1,3-Dioxo-perhydropyrrolo [1,2-
c] imidazol-2-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid ((4S) -4-beta
Benzyl-2,5-dioxoimidazolidin-1-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid ((4R) -4-benzyl-2,5-dioxoimid
Dazolidin-1-yl) amide, 5-chloro-1H-i
Ndole-2-carboxylic acid (2,4-dioxoimidazole
Zolidin-3-yl) amide, 5-chloro-1H-yne
Dole-2-carboxylic acid (1-methyl-2,5-dio
Xo-4-phenylimidazolidin-1-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(2,4-dioxo-1- (4-fluorophenyl) ii
Midazolidin-3-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid (2,5-dioxo-4
-(2-Fluorophenyl) imidazolidin-1-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (2,5-dioxo-4- (2-thienyl) yl
Midazolidin-1-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid (2,5-dioxo-4
-(4-Fluorophenyl) imidazolidin-1-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (2,5-dioxo-4- (4-chlorophenyl)
Ru) imidazolidin-1-yl) amide, 5-chloro-
1H-indole-2-carboxylic acid ((4S) -2,
5-dioxo-4- (4-hydroxyphenyl) imidazole
Zolidin-1-yl) amide, 5-chloro-1H-yne
Dole-2-carboxylic acid ((4S) -2,5-dioki
So-4- (4-methoxyphenyl) imidazolidine-1
-Yl) amide, 5-chloro-1H-indole-2-
Carboxylic acid ((4R) -2,5-dioxo-4- (4
-Methoxyphenyl) imidazolidin-1-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
2- (anilinocarbonyl) hydrazide, 5-chloro-
1H-indole-2-carboxylic acid 2- (phenylthio
Ocarbonyl) hydrazide, 5-chloro-1H-indo
2-carboxylic acid 2- (2-phenylacetyl)
Hydrazide, 5-chloro-1H-indole-2-cal
Boronic acid 2- (2-oxo-2-phenylacetyl) hi
Dorazide, 5-chloro-1H-indole-2-carb
2-((2-fluorophenyl) aminocarbonic acid
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2-((3-fluorophenyl) aminoca
Lubonyl) hydrazide, 5-chloro-1H-indole
-2-carboxylic acid 2-((4-fluorophenyl) a
Minocarbonyl) hydrazide, 5-chloro-1H-yne
Dole-2-carboxylic acid 2- (anilinocarbonyl)
-2-Methylhydrazide, 5-chloro-1H-indole
2-carboxylic acid 2-((2-chloroanilino) ca
Lubonyl) hydrazide, 5-chloro-1H-indole
-2-carboxylic acid 2-((3-chloroanilino) car
Bonyl) hydrazide, 5-chloro-1H-indole-
2-carboxylic acid 2-((4-chloroanilino) carbo
Nyl) hydrazide, 5-chloro-1H-indole-2
-Carboxylic acid 2-((1-phenylcyclopropane)
Carbonyl) hydrazide, 5-chloro-1H-indole
2-carboxylic acid 2-((1-phenylcyclopen
(Tan) carbonyl) hydrazide, 5-chloro-1H-i
And 2-carboxylic acid 2-((1-phenylcyclo
Rohexane) carbonyl) hydrazide, 5-chloro-1
H-indole-2-carboxylic acid 2- (2-phenyl
Propanoyl) hydrazide, 5-chloro-1H-indo
2-carboxylic acid 2- (3-hydroxy-2-fur
Phenylpropanoyl) hydrazide, 5-chloro-1H-
Indole-2-carboxylic acid 2- (2-methyl-2-
Phenylpropanoyl) hydrazide, 5-chloro-1H
-Indole-2-carboxylic acid 2-((2S) -2-
Amino-2-phenylacetyl) hydrazide, N- (2
-(2- (5-chloro-1H-indole-2-carb
Nyl) hydrazino) -2-oxo-1-phenylethyl
) Acetamide, 2-morpholinoethyl (2-
((2- (5-chloro-1H-indole-2-carb
Nyl) hydrazino) carbonyl) phenyl) carbame
P-toluenesulfonate, 2-amino-4,5-
Difluorobenzoic acid 2- (5-methyl-1H-indo)
2-carbonyl) hydrazide benzene sulfone
Acid salt, 2-amino-4-fluorobenzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Debenzene sulfonate, 3-dimethylaminobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide methanesulfonate, 2-amino-
4-Fluorobenzoic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide hydrochloride, 2-a
Mino-4-fluorobenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide p-tolu
Ensulfonate, 2-amino-4-fluorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
) Hydrazide p-toluenesulfonate, 2-ami
No-4-fluorobenzoic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide p-tolue
Sulfonate, 2-amino-4-fluorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
) Hydrazide p-toluenesulfonate, 2-ami
2-benzoic acid 2- (5-methyl-1H-indole-2)
-Carbonyl) hydrazide p-toluenesulfonic acid
Salt, 2-aminobenzoic acid 2- (5-methyl-1H-i)
Ndol-2-carbonyl) hydrazide benzenesul
Phonoate, 2-amino-4-fluorobenzoic acid 2-
(5-methyl-1H-indole-2-carbonyl) hi
Dolazide benzenesulfonate, 2-aminobenzoic acid
2- (5-chloro-1H-indole-2-carboni
) Hydrazide p-toluenesulfonate, 5-chloro
B-1H-indole-2-carboxylic acid 2-((2-
Chlorophenyl) -imino-methyl) hydrazide meta
Sulfonate, 5-chloro-1H-indole-2-
Carboxylic acid 2-((2-chlorophenyl) -imino-
Methyl) hydrazide p-toluenesulfonate, 5-
Chloro-1H-indole-2-carboxylic acid 2-
((2-chlorophenyl) -imino-methyl) hydrazide
Dehydrochloride, 5-chloro-1H-indole-2-cal
Boronic acid 2- (imino-phenyl-methyl) hydrazide
Methanesulfonate, 5-chloro-1H-indole
-2-carboxylic acid 2-((2-chlorophenyl) -i
Mino-methyl) hydrazide butenedioate, 5-chloro
-1 H-indole-2-carboxylic acid 2-((2-f
Luorophenyl) -imino-methyl) hydrazide hydrochloric acid
Salt, 5-chloro-1H-indole-2-carboxylic acid
2-((2-fluorophenyl) -imino-methyl) hi
Dolazide methanesulfonate, 5-chloro-1H-ii
Ndole-2-carboxylic acid 2-((1-imino-2-
Phenylethyl) hydrazide methanesulfonate, 5
-Chloro-1H-indole-2-carboxylic acid 2-
((3-Fluorophenyl) -imino-methyl) hydra
Zido hydrochloride, 5-chloro-1H-indole-2-ca
Rubonic acid 2-((3,4-difluorophenyl) -i
Mino-methyl) hydrazide methanesulfonate, 5-
Chloro-1H-indole-2-carboxylic acid 2- (a
Mino- (2-methoxyphenyl) -methyl) hydrazide
Methanesulfonate, 5-chloro-1H-indole
2-carboxylic acid 2-((2,6-difluorophenyl
) -Imino-methyl) hydrazide methanesulfonic acid
Salt, 5-chloro-1H-indole-2-carboxylic acid
2-((2,4-difluorophenyl) -imino-methyl
) Hydrazide methanesulfonate, 5-chloro-1
H-indole-2-carboxylic acid 2-((1,2-di
Methyl-1H-pyrrol-5-yl) -imino-methyl
Le) hydrazide methanesulfonate, 2-aminobenzoate
Aromatic acid 2- (5-methyl-1H-indole-2-cal
Bonyl) hydrazide p-toluenesulfonate, 2-
Aminobenzoic acid 2- (5-methyl-1H-indole)
-2-Carbonyl) hydrazide benzene sulfonic acid
Salt and 2-amino-4-fluorobenzoic acid 2-
(5-methyl-1H-indole-2-carbonyl) hi
Selected from the group consisting of dolazide benzene sulfonate
Indole compound according to [1], which is pharmaceutically acceptable
Salt or prodrug. [10] Benzoic acid 2- (5-chloro-1H-indo)
2-carbonyl) hydrazide, 2-aminobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 2-hydroxybenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 3- (2- (2- (5-chloro-1H-indole
L-2-carbonyl) hydrazinocarbonyl) phenyl
Carbamoyloxy) -2,2-dimethylpropion
Acid, benzoic acid 2- (5-chloro-1H-indole-
2-carbonyl) -1-methylhydrazide, benzoic acid
2- (1-acetyl-5-chloro-1H-indole-
2-carbonyl) hydrazide, 5-chloro-1H-yne
Dole-2-carboxylic acid 2- (imino-phenyl-meth)
Tyl) hydrazide, 5-aminothiazole-4-carbo
Acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, benzoic acid 2- (5-fluoro-
1H-indole-2-carbonyl) hydrazide, shik
Rohexanecarboxylic acid 2- (5-fluoro-1H-i)
Ndole-2-carbonyl) hydrazide, thiophene-
2-carboxylic acid 2- (5-fluoro-1H-indole
2-L-carbonyl) hydrazide, 4-nitrobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-methylbenzoic acid 2- (5-chloro)
-1H-indole-2-carbonyl) hydrazide,
4-Methylbenzoic acid 2- (5-chloro-1H-indo
2-carbonyl) hydrazide, 2-methoxybenzo
Aromatic acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 3-methoxybenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 4-methoxybenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 3-methyi
Le benzoic acid 2- (5-chloro-1H-indole-2
-Carbonyl) hydrazide, 2-chlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-chlorobenzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 4-ku
Lolobenzoic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 4- (2- (5-chloro
-1H-indole-2-carbonyl) hydrazinocar
Bonyl) benzoic acid methyl ester, cyclohexanecal
Boronic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 2,4-dichlorobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2,6-dichlorobenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
De, 2,4-difluorobenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, bif
Phenyl-2-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, 3-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 4-fluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-trifluoromethylbenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 4-trifluoromethylbenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
De, 2-trifluoromethylbenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
Benzoic acid 2- (5-methyl-1H-indole-2-
Carbonyl) hydrazide, benzoic acid 2- (5-chloro)
-3-Methyl-1H-indole-2-carbonyl) hi
Dolazide, benzoic acid 2- (5,7-dichloro-1H-
Indole-2-carbonyl) hydrazide, 2-amino
Benzoic acid 2- (5-isopropyl-1H-indole)
-2-Carbonyl) hydrazide, 2-amino-4-fur
Orobenzoic acid 2- (5-isopropyl-1H-indo)
2-carbonyl) hydrazide, 2-aminobenzoic acid
Acid 2- (5-Fluoro-1H-indole-2-cal
Bonyl) hydrazide, 2-aminobenzoic acid 2- (6-
Chloro-1H-indole-2-carbonyl) hydrazide
3-amino-4- (2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazinocarbonyl) rest
Aromatic acid methyl ester, 3-aminoisonicotinic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, isonicotinic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide, nicotinic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, pyridine-2-carboxylic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 3- (dimethylamino) benzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
N- (3- (2- (5-chloro-1H-indole
-2-carbonyl) hydrazinocarbonyl) phenyl)
Acetamide, N- (2- (2- (5-chloro-1H-
Indole-2-carbonyl) hydrazinocarbonyl)
Phenyl) acetamide, 4-fluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl)-
2-methylhydrazide, 2- (2- (2- (5-chloro
-1H-indole-2-carbonyl) hydrazinocar
Bonyl) phenoxy) acetic acid methyl ester, 2- (2
-(2- (5-chloro-1H-indole-2-carb
Nil) hydrazinocarbonyl) phenoxy) acetic acid, 2
-(Dimethylamino) benzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 2-
(2- (5-chloro-1H-indole-2-carboni
Le) hydrazinocarbonyl) phenoxy-N, N-dime
Cylacetamide, 2-methylaminobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2-amino-4-chlorobenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 2-amino-6-chlorobenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
2-amino-3-chlorobenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
2-Amino-5-chlorobenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 4-
Cyanobenzoic acid 2- (5-chloro-1H-indole
-2-carbonyl) hydrazide, 4- (1H-tetrazo
Rol-5-yl) benzoic acid 2- (5-chloro-1H-)
Indole-2-carbonyl) hydrazide, 3- (1H
-Tetrazol-5-yl) benzoic acid 2- (5-chloro)
-1H-indole-2-carbonyl) hydrazide,
2- (2- (2- (5-chloro-1H-indole-2
-Carbonyl) hydrazinocarbonyl) anilino) vinegar
Acid, 2-aminobenzoic acid 2- (5-methyl-1H-i)
Ndole-2-carbonyl) hydrazide, 2-amino-
4-Fluorobenzoic acid 2- (5-methyl-1H-yne
Dole-2-carbonyl) hydrazide, methyl 2-
(2- (5-methyl-1H-indole-2-carbonyl
Le) hydrazinocarbonyl) phenyl) carbamate,
2- (2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazinocarbonyl) phenyl dimethyl carbonate
Lubamate, 2-aminobenzoic acid 2- (5-ethyl-
1H-indole-2-carbonyl) hydrazide, 2-
Amino-4,5-difluorobenzoic acid 2- (5-methyl
Ru-1H-indole-2-carbonyl) hydrazide,
2- (2-hydroxyethoxy) benzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
2- (3- (2- (5-chloro-1H-indole
-2-Carbonyl) hydrazinocarbonyl) phenoki
Si) acetic acid methyl ester, 2- (3- (2- (5-chloro
B-1H-indole-2-carbonyl) hydrazinoca
Lubonyl) phenoxy) acetic acid, 2- (3- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) phenoxy) -N, N-dimethylacetate
Amide, N- (1,2,3,4-tetrahydro-7-di
Toro-2,4-dioxoquinazolin-3-yl) -5-
Chloro-1H-indole-2-carboxylic acid amide, 2
-Methylthiazole-4-carboxylic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
4- (2H- [1,2,4] triazol-3-yl) an
Benzoic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 3- (2H- [1,2,4] tri
Azol-3-yl) benzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 1,3
-Dihydroxy-2-propyl (2- (2- (5-
Lolo-1H-indole-2-carbonyl) hydrazino
Carbonyl) phenyl) carbamate, 3-((2-
(2- (5-chloro-1H-indole-2-carboni
Le) hydrazinocarbonyl) phenyl) carbamoylo
Xy) -2,2-dimethylpropionic acid, thiophene-
2-carboxylic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide, furan-2-carvone
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 2,6-dichloronicotinic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 1H-pyrrole-2-carboxylic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 1H-imidazole-4-carboxylic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, pyrazine-2-carboxylic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, thio
Phen-3-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, furan-3-
Carboxylic acid 2- (5-chloro-1H-indole-2
-Carbonyl) hydrazide, 5-chlorothiophene-2
-Carboxylic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 3-chlorothiophene-
2-carboxylic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide, 1-methyl-1H-pi
Roll-2-carboxylic acid 2- (5-chloro-1H-i)
Ndol-2-carbonyl) hydrazide, 5-methylthio
Offene-2-carboxylic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide, 3-methyl
Thiophene-2-carboxylic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 2,6-
Difluorobenzoic acid 2- (5-chloro-1H-indo
2-carbonyl) hydrazide, 2,3-difluor
B-benzoic acid 2- (5-chloro-1H-indole-2)
-Carbonyl) hydrazide, 5-chloro-1H-indo
2-carboxylic acid 2- (naphthalene-1-carbohydrate)
Nyl) hydrazide, 3,4,5-trifluorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2,3,4,5-tetrafluorobenzoate
Aromatic acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 2-amino-4-methylbenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-amino-4-fluorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-amino-5-methylbenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-amino-6-methylbenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2-amino-3-methylbenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 2-amino-4,5-difluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-aminothiophene-2-carboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-aminobenzoic acid 2- (5-bromo-
1H-indole-2-carbonyl) hydrazide, 2-
Amino-4-fluorobenzoic acid 2- (5-bromo-1
H-indole-2-carbonyl) hydrazide, 1H-
Pyrazole-4-carboxylic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, methyl
(2- (2- (5-fluoro-1H-indole-2-
Carbonyl) hydrazinocarbonyl) phenyl) carba
Mate, 1-methyl-1H-pyrrole-2-carboxylic acid
2- (5-methyl-1H-indole-2-carboni
Le) hydrazide, thiophene-3-carboxylic acid 2-
(5-methyl-1H-indole-2-carbonyl) hi
Dorazide, 4H-thieno [3,2-b] pyrrole-5-
Carboxylic acid 2- (5-chloro-1H-indole-2
-Carbonyl) hydrazide, phenyl (2- (2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazinocarbonyl) phenyl) carbamate, benzi
Ru (2- (2- (5-chloro-1H-indole-2
-Carbonyl) hydrazinocarbonyl) phenyl) calc
Bamate, 2-hydroxyethyl (2- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) phenyl) carbamate, 3-hydroxy
Cypropyl (2- (2- (5-chloro-1H-indo
2-carbonyl) hydrazinocarbonyl) pheny
Carbamate, 2-((2- (5-chloro-1H-
Indole-2-carbonyl) hydrazinocarbonyl)
Phenyl) carbamoyloxy) acetic acid, 2-((2-
(2- (5-chloro-1H-indole-2-carboni
Le) hydrazinocarbonyl) phenyl) carbamoylo
Xymethyl) -2-methylmalonic acid, methyl 2- (2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazinocarbonyl) phenyl carbamate, cyclo
Hexanecarboxylic acid 2- (5-chloro-1H-indo)
2-carbonyl) -1-methylhydrazide, thio
Phen-2-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) -1-methylhydrazide,
Benzoic acid 2- (1H-indole-2-carbonyl)
Hydrazide, benzoic acid 2- (5-chloro-1-methyl)
-1H-indole-2-carbonyl) hydrazide, cheap
Benzoic acid 2- (5-methoxy-1H-indole-2-
Carbonyl) hydrazide, benzoic acid 2- (5-isop
Ropyr-1H-indole-2-carbonyl) hydrazide
De, benzoic acid 2- (5-nitro-1H-indole-
2-carbonyl) hydrazide, benzoic acid 2- (5-
Benzyloxy-1H-indole-2-carbonyl) hi
Dolazide, benzoic acid 2- (6-chloro-1H-india
2-carbonyl) hydrazide, 6H-thieno
[2,3-b] Pyrrole-5-carboxylic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((2-Fluorophenyl) -imino-methyl) hi
Dorazide, 5-chloro-1H-indole-2-carb
Acid 2-((3-fluorophenyl) -imino-methyl
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2-((4-fluorophenyl) -imino
-Methyl) hydrazide, 5-chloro-1H-indole
2-carboxylic acid 2- (imino- (p-tolyl) -me
Chill) hydrazide, 5-chloro-1H-indole-2
-Carboxylic acid 2-((4-chlorophenyl) -imino
-Methyl) hydrazide, 5-chloro-1H-indole
-2-carboxylic acid 2-((3-chlorophenyl) -i
Mino-methyl) hydrazide, 5-chloro-1H-indo
-2-carboxylic acid 2-((2-chlorophenyl)
-Imino-methyl) hydrazide, 5-chloro-1H-i
Ndole-2-carboxylic acid 2- (imino- (o-tri
) -Methyl) hydrazide, 5-chloro-1H-indo
2-carboxylic acid 2- (imino- (m-tolyl)
-Methyl) hydrazide, 5-chloro-1H-indole
2-carboxylic acid 2- (imino- (thiophene-2-
Yl) -methyl) hydrazide, 5-chloro-1H-yne
Dole-2-carboxylic acid 2- (imino- (pyridine-
2-yl) -methyl) hydrazide, 5-chloro-1H-
Indole-2-carboxylic acid 2-((furan-2-i
) -Imino-methyl) hydrazide, 5-chloro-1H
-Indole-2-carboxylic acid 2-((2-chloro-
6-Fluorophenyl) -imino-methyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (2-trifluoromethylphenyl)-
Methyl) hydrazide, 5-chloro-1H-indole-
2-carboxylic acid 2- (imino- (pyrazin-2-i
) -Methyl) hydrazide, 3-aminobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 3-methoxybenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 5-
Amino-2-methylthiazole-4-carboxylic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2-morpholinoethyl (2-((2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Dino) carbonyl) phenyl) carbamate p-tolu
Ensulfonate, 2-amino-4,5-difluoro ammonium
Benzoic acid 2- (5-methyl-1H-indole-2-ca)
Rubonyl) hydrazide benzene sulfonate, 2-a
Mino-4-fluorobenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide benzene
Sulfonate, 3-dimethylaminobenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido methanesulfonate, 2-amino-4-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide hydrochloride, 2-amino-4-phenyl
Luorobenzoic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide p-toluene sulfone
Acid salt, 2-amino-4-fluorobenzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Dop-toluenesulfonate, 2-amino-4-ful
Orobenzoic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide p-toluenesulfonic acid
Salt, 2-amino-4-fluorobenzoic acid 2- (5-
Lolo-1H-indole-2-carbonyl) hydrazide
p-toluenesulfonate, 2-aminobenzoic acid 2
-(5-methyl-1H-indole-2-carbonyl)
Hydrazide p-toluenesulfonate, 2-aminoammonium salt
Benzoic acid 2- (5-methyl-1H-indole-2-ca)
Rubonyl) hydrazide benzene sulfonate, 2-a
Mino-4-fluorobenzoic acid 2- (5-methyl-1H)
-Indole-2-carbonyl) hydrazide benzene
Sulfonate, 2-aminobenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide p
-Toluenesulfonate, 5-chloro-1H-indole
2-carboxylic acid 2-((2-chlorophenyl)-
Imino-methyl) hydrazide methanesulfonate, 5
-Chloro-1H-indole-2-carboxylic acid 2-
((2-chlorophenyl) -imino-methyl) hydrazide
Dop-toluenesulfonate, 5-chloro-1H-i
And 2-carboxylic acid 2-((2-chlorophenyl
) -Imino-methyl) hydrazide hydrochloride, 5-chloro
B-1H-indole-2-carboxylic acid 2- (imino
-Phenyl-methyl) hydrazide methanesulfonic acid
Salt, 5-chloro-1H-indole-2-carboxylic acid
2-((2-chlorophenyl) -imino-methyl) hydr
Radiz butene diacid salt, 5-chloro-1H-indole
-2-carboxylic acid 2-((2-fluorophenyl)-
Imino-methyl) hydrazide hydrochloride, 5-chloro-1
H-indole-2-carboxylic acid 2-((2-fluor
Rophenyl) -imino-methyl) hydrazide methan
Ruphonate, 5-chloro-1H-indole-2-cal
Boronic acid 2-((1-imino-2-phenylethyl) hi
Dolazide methanesulfonate, 5-chloro-1H-ii
Ndole-2-carboxylic acid 2-((3-fluorophen
Nyl) -imino-methyl) hydrazide hydrochloride, 5-
Lolo-1H-indole-2-carboxylic acid 2-
((3,4-difluorophenyl) -imino-methyl)
Hydrazide methanesulfonate, 5-chloro-1H-
Indole-2-carboxylic acid 2- (imino- (2-me
Toxyphenyl) -methyl) hydrazide methanesulfo
Phosphate, 5-chloro-1H-indole-2-carboxylic acid
Acid 2-((2,6-difluorophenyl) -imino-
Methyl) hydrazide methanesulfonate, 5-chloro
-1H-indole-2-carboxylic acid 2-((2,4
-Difluorophenyl) -imino-methyl) hydrazide
Methanesulfonate, 5-chloro-1H-indole
2-carboxylic acid 2-((1,2-dimethyl-1H-
Pyrrol-5-yl) -imino-methyl) hydrazide
Methanesulfonate, 2-aminobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide
Dop-toluenesulfonate, 2-aminobenzoic acid
2- (5-methyl-1H-indole-2-carboni
) Hydrazide benzene sulfonate, and 2-a
Mino-4-fluorobenzoic acid 2- (5-methyl-1H)
-Indole-2-carbonyl) hydrazide benzene
The sulfonate according to claim 1, which is selected from the group consisting of
Indole compound, pharmaceutically acceptable salt or prod thereof
Rugg. [11] 2-morpholinoethyl (2-((2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Dino) carbonyl) phenyl) carbamate p-tolu
Ensulfonate, 2-amino-4,5-difluoro ammonium
Benzoic acid 2- (5-methyl-1H-indole-2-ca)
Rubonyl) hydrazide benzene sulfonate, 2-a
Mino-4-fluorobenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide benzene
Sulfonate, 3-dimethylaminobenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido methanesulfonate, 2-amino-4-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide hydrochloride, 2-amino-4-phenyl
Luorobenzoic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide p-toluene sulfone
Acid salt, 2-amino-4-fluorobenzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Dop-toluenesulfonate, 2-amino-4-ful
Orobenzoic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide p-toluenesulfonic acid
Salt, 2-amino-4-fluorobenzoic acid 2- (5-
Lolo-1H-indole-2-carbonyl) hydrazide
p-toluenesulfonate, 2-aminobenzoic acid 2
-(5-methyl-1H-indole-2-carbonyl)
Hydrazide p-toluenesulfonate, 2-aminoammonium salt
Benzoic acid 2- (5-methyl-1H-indole-2-ca)
Rubonyl) hydrazide benzene sulfonate, 2-a
Mino-4-fluorobenzoic acid 2- (5-methyl-1H)
-Indole-2-carbonyl) hydrazide benzene
Sulfonate, 2-aminobenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide p
-Toluenesulfonate, 5-chloro-1H-indole
2-carboxylic acid 2-((2-chlorophenyl)-
Imino-methyl) hydrazide methanesulfonate, 5
-Chloro-1H-indole-2-carboxylic acid 2-
((2-chlorophenyl) -imino-methyl) hydrazide
Dop-toluenesulfonate, 5-chloro-1H-i
And 2-carboxylic acid 2-((2-chlorophenyl
) -Imino-methyl) hydrazide hydrochloride, 5-chloro
B-1H-indole-2-carboxylic acid 2- (imino
-Phenyl-methyl) hydrazide methanesulfonic acid
Salt, 5-chloro-1H-indole-2-carboxylic acid
2-((2-chlorophenyl) -imino-methyl) hydr
Radiz butene diacid salt, 5-chloro-1H-indole
-2-carboxylic acid 2-((2-fluorophenyl)-
Imino-methyl) hydrazide hydrochloride, 5-chloro-1
H-indole-2-carboxylic acid 2-((2-fluor
Rophenyl) -imino-methyl) hydrazide methan
Ruphonate, 5-chloro-1H-indole-2-cal
Boronic acid 2-((1-imino-2-phenylethyl) hi
Dolazide methanesulfonate, 5-chloro-1H-ii
Ndole-2-carboxylic acid 2-((3-fluorophen
Nyl) -imino-methyl) hydrazide hydrochloride, 5-
Lolo-1H-indole-2-carboxylic acid 2-
((3,4-difluorophenyl) -imino-methyl)
Hydrazide methanesulfonate, 5-chloro-1H-
Indole-2-carboxylic acid 2- (imino- (2-me
Toxyphenyl) -methyl) hydrazide methanesulfo
Phosphate, 5-chloro-1H-indole-2-carboxylic acid
Acid 2-((2,6-difluorophenyl) -imino-
Methyl) hydrazide methanesulfonate, 5-chloro
-1H-indole-2-carboxylic acid 2-((2,4
-Difluorophenyl) -imino-methyl) hydrazide
Methanesulfonate, 5-chloro-1H-indole
2-carboxylic acid 2-((1,2-dimethyl-1H-
Pyrrol-5-yl) -imino-methyl) hydrazide
Methanesulfonate, 2-aminobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide
Dop-toluenesulfonate, 2-aminobenzoic acid
2- (5-methyl-1H-indole-2-carboni
) Hydrazide benzene sulfonate, and 2-a
Mino-4-fluorobenzoic acid 2- (5-methyl-1H)
-Indole-2-carbonyl) hydrazide benzene
[1] The inn selected from the group consisting of sulfonates
Dole compound, its pharmaceutically acceptable salt or prodrug
Gu. [12] The inn according to any one of [1] to [11].
Dole compound, its pharmaceutically acceptable salt or prodrug
And a pharmaceutically acceptable carrier
object. [13] The inn according to any one of [1] to [11]
Dole compound, its pharmaceutically acceptable salt or prodrug
HLGP containing a carrier and a pharmaceutically acceptable carrier
a inhibitor. [14] The inn according to any one of [1] to [11]
Dole compound, its pharmaceutically acceptable salt or prodrug
Diabetes and a pharmaceutically acceptable carrier
Medical treatment. [15] Note on [14] for combined use with therapeutic drug for hyperlipidemia
The listed pharmaceutical compositions. [16] The drug for treating hyperlipidemia is a statin drug
The pharmaceutical composition according to [15]. [17] Statins are lovastatin, simva
Statin, pravastatin, fluvastatin, atorva
Selected from the group consisting of statins and cerivastatin
The pharmaceutical composition according to [16]. [18] Insulin preparations, sulfonylurea drugs, insulin
Phosphorus secretagogues, sulfonamides, biguanides,
Is it an α-glucosidase inhibitor and insulin sensitizer?
Diabetes drug and HLGPa inhibitor selected from the group consisting of
A pharmaceutical composition for treating or preventing diabetes, which comprises a combination of
object. [19] Antidiabetic agents include insulin and glibencra
Mid, tolbutamide, glyclopyramide, acetohexa
Mid, glimepiride, tolazamide, gliclazide, nate
Glinide, glybuzole, metformin hydrochloride, bufo hydrochloride
Lumin, voglibose, acarbose and piogli hydrochloride
[18] the diabetes selected from the group consisting of tazone
A therapeutic or prophylactic pharmaceutical composition. [20] HLPa inhibitors are [1] to [11]
Indole compound described in any of the above, and its pharmaceutically acceptable
[18] or [19] which is a salt or prodrug of
Remedy for diabetes.

The definition of each substituent used in the present specification is as follows. A "halogen atom" is a chlorine atom,
Examples thereof include bromine atom and fluorine atom. R ² is preferably a chlorine atom, R ³ is preferably a chlorine atom,
A bromine atom and a fluorine atom, R ¹¹ , R ¹² ,
R ¹³ , R ¹⁴ and R ¹⁵ are preferably a chlorine atom or a fluorine atom, and R ^{16b to} R ¹⁶ⁿ and R ¹⁶
Preferably in ^17b to R ^{17 n} is chlorine atom,
R ³⁶ and R ³⁷ are preferably a chlorine atom and a fluorine atom.

"C_1-6An "alkyl group" has 1 to 1 carbon atoms.
6 linear or branched alkyl groups, such as
For example, methyl group, ethyl group, propyl group, isopropyl group,
Butyl group, isobutyl group, sec-butyl group, tert
-Butyl group, pentyl group, isopentyl group, neopentyl
And a tert-pentyl group or a hexyl group,
Preferably, it may be a straight chain or branched chain having 1 to 4 carbon atoms.
It is a rukyll group. Particularly preferably, a methyl group, an ethyl group,
Alternatively, it is an isopropyl group. R¹In the
Is a chill group, R^ThreeIs preferably a methyl group or ethyl
R group or isopropyl group, R^FourPreferred
Is a methyl group, R⁵And preferably a methyl group
Yes, R⁶Is preferably a methyl group and R⁸To
Is preferably a methyl group and R⁹And R¹⁰To
And preferably a methyl group, R¹¹, R¹², R
^Thirteen, R¹⁴And R¹⁵And preferably a methyl group
Yes, R^16b~ R¹⁶ⁿAnd R^17b~ R¹⁷ⁿTo
And preferably a methyl group, R²⁰And R²¹To
And preferably a methyl group or an ethyl group, R²⁵Over
And R²⁶Is preferably a methyl group or an ethyl group.
R²⁸And R²⁹Is preferably a methyl group or
Is an ethyl group, R^ThirtyAnd preferably a methyl group,
Ethyl group, propyl group, isopropyl group, butyl group, a
Sobutyl group, sec-butyl group, tert-butyl group,
Pentyl group, isopentyl group, neopentyl group or te
rt-pentyl group, R³¹, R^{31 '}, R³²Over
And R^{32 '}Is preferably a methyl group or an ethyl group
Yes, R³³Is preferably a methyl group and R
³⁵Is preferably a methyl group and R³⁶And R
³⁷Is preferably a methyl group and R³⁹And R
⁴⁰Is preferably a methyl group and R⁴¹smell
And preferably a methyl group, R⁴², R^{42 '}, R
^{42 ''}And R⁴³Is preferably a methyl group
R⁴⁴And R^{44 '}And preferably a methyl group,
An ethyl group, a propyl group or an isopropyl group, R
⁴⁵Is preferably a methyl group.

"C _1-6 alkyl group" for R ³⁰
May be substituted with a hydroxyl group, a trifluoromethyl group, an aryl group which may have a substituent (synonymous with the following “aryl group”, preferably phenyl group), a morpholino group or a carboxyl group, and the substitution position thereof Is not particularly limited as long as it can be replaced. Examples of the C _1-6 alkyl group substituted with a hydroxyl group, a trifluoromethyl group, an aryl group which may have a substituent, a morpholino group or a carboxyl group include a 2-hydroxyethyl group, a 3-hydroxypropyl group, 4-hydroxybutyl group, 2,3-dihydroxypropyl group; 2-carboxypropyl group or 2,2
-Dicarboxypropyl group; 2,2,2-trifluoroethyl group; benzyl group; morpholinomethyl group and the like, and preferably 2,3-dihydroxypropyl group or 2,2-dicarboxypropyl group.

The "C _1-6 alkyl group" for R ⁴⁴ and R ^{44 '} may be substituted with a carboxyl group or a C _2-7 alkoxycarbonyl group (as defined below), and the substitution position is substitutable. There is no particular limitation. As the C _1-6 alkyl group substituted with a carboxyl group or a C _2-7 alkoxycarbonyl group, a carboxymethyl group,
A methoxycarbonylmethyl group is preferred.

"C_1-6"Alkoxy group" has 1 carbon atom.
~ 6 straight or branched chain alkoxy groups, for example
Toxy group, ethoxy group, propoxy group, isopropoxy group
Group, butoxy group, tert-butoxy group, pentyloxy group
Si group, tert-pentyloxy group or hexyloxy
Group, preferably a straight or branched chain having 1 to 4 carbon atoms
An alkoxy group, for example, a methoxy group, an ethoxy group,
Isopropoxy group, butoxy group, tert-butoxy group
Is. Particularly preferred is a methoxy group or an ethoxy group.
It R^ThreeIs preferably a methoxy group,
R¹¹, R¹², R^{1 Three}, R¹⁴And R¹⁵Good in
Preferably, it is a methoxy group or an ethoxy group, and R ^16b~
R¹⁶ⁿAnd R^17b~ R¹⁷ⁿIn the
A toxy group, R¹⁹Is preferably a methoxy group
And R²²And R^{22 '}In preferably met
A xy group, R²⁴And preferably a methoxy group,
An ethoxy group, a propoxy group or an isopropoxy group
R³⁴Is preferably a methoxy group, and R is
³⁶And R³⁷Is preferably a methoxy group,
R³⁹And R⁴⁰Is preferably a methoxy group
It

The "C _2-7 alkoxycarbonyl group" means that the alkyl portion has 1 to 6 carbon atoms (preferably 1 to 4 carbon atoms).
And a linear or branched alkoxycarbonyl group, for example, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, tert-butoxy group. Carbonyl group,
Examples include a pentyloxycarbonyl group and hexyloxycarbonyl. Preferably a methoxycarbonyl group,
It is an ethoxycarbonyl group or a tert-butoxycarbonyl group. R ⁵ is preferably a methoxycarbonyl group, R ¹⁸ is preferably a methoxycarbonyl group or a tert-butoxycarbonyl group, and R
Preferably at ³⁶ and ^{R 3 7} is a methoxycarbonyl ^group, preferably at ^{R 39} and ^{R 40} are methoxycarbonyl ^group, preferably at ^{R 44} and ^{R 44 'is} a methoxycarbonyl group.

The "C _2-7 alkoxycarbonylamino group" means that the alkyl portion has 1 to 6 carbon atoms (preferably 1 carbon atom).
~ 4) and is a linear or branched alkoxycarbonylamino group, for example, a methoxycarbonylamino group, an ethoxycarbonylamino group, a propoxycarbonylamino group, an isopropoxycarbonylamino group, a butoxycarbonylamino group. , Isobutoxycarbonylamino group, tert-butoxycarbonylamino group, pentyloxycarbonylamino group, hexyloxycarbonylamino group and the like. Preferred is a methoxycarbonylamino group, an ethoxycarbonylamino group or a tert-butoxycarbonylamino group. R ⁹
And R ¹⁰ is preferably a methoxycarbonyl group or a tert-butoxycarbonylamino group, and R
²² and R ^{22 ′} are preferably tert-butoxycarbonylamino groups.

The "C _3-13 alkoxycarbonylalkyl group" means that both alkyl parts (alkoxy part and alkyl part) have 1 to 6 carbon atoms (preferably 1 to 4 carbon atoms) and are straight chain or branched chain. And represents an alkoxycarbonylalkyl group, for example, methoxycarbonylmethyl group, methoxycarbonylethyl group, ethoxycarbonylmethyl group, ethoxycarbonylethyl group, propoxycarbonylmethyl group, isopropoxycarbonylmethyl group, butoxycarbonylmethyl group, isobutoxycarbonyl group. Examples thereof include a methyl group, a tert-butoxycarbonylmethyl group, a pentyloxycarbonylmethyl group, and a hexyloxycarbonylmethyl group. Preferred is a methoxycarbonylmethyl group, an ethoxycarbonylmethyl group or a tert-butoxycarbonylmethyl group. R
^{In 20} and R ²¹ , a methoxycarbonylmethyl group is preferable.

"C _2-7 alkylcarbonyloxy group"
Means that the alkyl part has 1 to 6 carbon atoms (preferably 1 to 4 carbon atoms).
And a straight-chain or branched-chain alkylcarbonyloxy group, for example, methylcarbonyloxy group, ethylcarbonyloxy group, propylcarbonyloxy group, isopropylcarbonyloxy group, butylcarbonyloxy group, isobutylcarbonyloxy group. Base, te
Examples include rt-butylcarbonyloxy group, pentylcarbonyloxy group, hexylcarbonyloxy group and the like.
It is preferably a methylcarbonyloxy group, an ethylcarbonyloxy group or a tert-butylcarbonyloxy group. R ²³ is preferably a methylcarbonyloxy group, and R ³⁴ is preferably a methylcarbonyloxy group.

"C _1-6 hydroxyalkyl group" means
It is a group in which a linear or branched alkyl group having 1 to 6 carbon atoms (preferably 1 to 4 carbon atoms) is substituted with one or two or more hydroxyl groups, and the substitution position of the hydroxyl group is not particularly limited. For example, hydroxymethyl group; 1- or 2-hydroxyethyl group;
1-, 2- or 3-hydroxypropyl group;
-, 3- or 4-hydroxybutyl group; 1-, 2-, 3
-, 4- or 5-hydroxypentyl group; 1-, 2-,
3-, 4-, 5- or 6-hydroxyhexyl group; 2-
Hydroxy-2-methylethyl group; 1,2-dihydroxyethyl group and the like, and preferably 2-hydroxyethyl group or 1,2-dihydroxyethyl group. A hydroxymethyl group is preferable for R ⁹ and R ¹⁰ .

The "C _1-6 haloalkyl group" means a halogen atom having 1 or 2 or more linear or branched alkyl groups having 1 to 6 carbon atoms (preferably 1 to 4 carbon atoms) (as defined above). )
And the substitution position is not particularly limited. For example, trifluoromethyl group, 1- or 2-chloroethyl group, 1- or 2-bromoethyl group, 1- or 2
-Fluoroethyl group, 1-, 2- or 3-chloropropyl group, 1-, 2- or 3-bromopropyl group, 1-, 2
-Or 3-fluoropropyl group, 1-, 2-, 3- or 4-chlorobutyl group, 1-, 2-, 3- or 4-bromobutyl group, 1-, 2-, 3- or 4-fluorobutyl group Etc., preferably a trifluoromethyl group. R
^{In 11} , R ¹² , R ¹³ , R ¹⁴ and R ¹⁵ , a trifluoromethyl group is preferable.

The "C _1-6 alkylamino group" is an amino group mono-substituted by a linear or branched alkyl group having 1 to 6 carbon atoms (preferably 1 to 4 carbon atoms), and for example, A methylamino group, an ethylamino group, a propylamino group, a butylamino group, a pentylamino group, a hexylamino group and the like are preferable, and a methylamino group or an ethylamino group is preferable. R ²⁷ is preferably a methylamino group or an ethylamino group, R ³⁴ is preferably a methylamino group, and R ⁴¹ is preferably a methylamino group or an ethylamino group.

The "C _2-12 dialkylamino group" means
It is an amino group that is disubstituted with a linear or branched alkyl group having 1 to 6 carbon atoms (preferably 1 to 4 carbon atoms), and the alkyl moieties may be the same or different. For example, a dimethylamino group, a diethylamino group, a dipropylamino group, a dibutylamino group, a dipentylamino group, a dihexylamino group and the like are preferable, and a dimethylamino group or a diethylamino group is preferable. Preferably the R ^{2 2} and ^{R 22 'is} a dimethylamino ^group, preferably in ^{R 27} is a dimethylamino ^group, preferably in ^{R 34} is a dimethylamino ^group, preferably in ^{R 41} is dimethylamino group.

The "C _3-7 cycloalkyl group" means a cycloalkyl group having 3 to 7 carbon atoms (preferably 3 to 6 carbon atoms), specifically, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, A cyclohexyl group or a cycloheptyl group. Preferred is a cycloalkyl group having 3 to 6 carbon atoms, and specifically, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group. Particularly preferred is a cyclopropyl group or a cyclohexyl group. R ⁹ and R ¹⁰ are preferably a cyclopropyl group, a cyclopentyl group or a cyclohexyl group.

"Acyl group" means acetyl group, propio
Alkylcarbo groups such as nyl, butyryl and pivaloyl groups
Nyl group (preferably 1 to 6 carbon atoms in the alkyl part,
It is preferably 1 to 4 and is linear or branched);
Arylcarbonyl group such as benzoyl group and naphthoyl group
(The carbon number of the aryl portion is preferably 6 to 12, more preferably
It is preferably 6 to 10) and the like, and preferably acetyl
It is a ru basis. R¹Is preferably an acetyl group
R^ThreeIs preferably an acetyl group, R ²⁸
And R²⁹Is preferably an acetyl group.

The "aryl group" preferably has 6 to 6 carbon atoms.
Twelve, more preferably 6 to 10, for example, a phenyl group, a naphthyl group, etc., preferably a phenyl group. The aryl group includes a phenyl group, a haloalkyl group (the same as the above "C _1-6 haloalkyl group"), a halogen atom (as defined above), a C _1-6 alkyl group (as defined above), C _1-6 alkoxy group (as defined above), C _2-7 alkoxycarbonyl group (as _defined above), nitro group, cyano group, carboxyl group, hydroxyl group,
1 to 6 identical or different amino groups, C _1-6 alkylamino groups (as defined above) and diC _1-6 alkylamino groups (as _defined above for “C _2-12 dialkylamino group”) It may be substituted with a substituent, and the position of the substituent is arbitrary and is not particularly limited.
The phenyl group in the above-mentioned substituent may be further substituted with 1 to 6 same or different substituents selected from the above-mentioned group of substituents (excluding phenyl group). Specifically, a phenyl group substituted by the following same or different 1 to 3 substituents is preferable; examples of the substituent include a haloalkyl group such as a trifluoromethyl group; a chlorine atom, a bromine atom, and a fluorine atom. Halogen atom such as atom; C _1-6 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, tert-butyl group; methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, C _1-6 alkoxy group such as isobutoxy group, sec-butoxy group and tert-butoxy group;
C _2-7 alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group; nitro group; cyano group; carboxyl group; hydroxyl group; amino group; methylamino group, ethylamino group, propylamino group, butylamino group And other C _1-6 alkylamino groups; diC _1-6 alkylamino groups such as dimethylamino group, diethylamino group and dipropylamino group. R
⁸ is preferably a phenyl group, and R ¹¹ , R
¹² , R ¹³ , R ¹⁴ and R ¹⁵ are preferably phenyl groups, R ¹⁹ are preferably phenyl groups, and R ²⁸ and R ²⁹ are preferably phenyl groups, R ³¹ , R ³⁰ , R ^{31 ′.} , R ³² and R
^{32 ′} is preferably a phenyl group, R ³³ is preferably a phenyl group, and R ³⁸ is preferably a phenyl group optionally substituted with a halogen atom or a C _1-6 alkyl group (particularly, a phenyl group and chlorophenyl). Group, fluorophenyl group, tolyl group), preferably a phenyl group for R ⁴² , R ^{42 ′} , R ^{42 ″} and R ⁴³ , and a phenyl group optionally substituted with a halogen atom for R ⁴⁵ . (Especially, a phenyl group and a fluorophenyl group), and R ⁴⁶
And R ^{46 ′} is preferably a phenyl group which may be substituted with a halogen atom, a hydroxy group or a C _1-6 alkoxy group (in particular, a phenyl group, a fluorophenyl group, a chlorophenyl group, a hydroxyphenyl group and a methoxyphenyl group). is there.

The "aryloxy group" preferably has 6 to 12 carbon atoms, more preferably 6 to 10 carbon atoms, and is, for example, a phenoxy group, a naphthyloxy group or the like, preferably a phenoxy group. The aryl group in the aryloxy group is a phenyl group, a haloalkyl group (the same as the above “C _1-6 haloalkyl group”), a halogen atom (synonymous with the above), a C _1-6 alkyl group (the above _{synonymous), C 1-6} alkoxy group (as defined _{above), C 2-7} alkoxycarbonyl group (as defined above), a nitro group, a cyano group, a carboxyl group, a hydroxyl group,
1 to 6 identical or different groups selected from an amino group, a C _1-6 alkylamino group (as defined above) and a diC _1-6 alkylamino group (as _defined above for “C _2-12 dialkylamino group”) It may be substituted with a substituent. The phenyl group in the above-mentioned substituent may be further substituted with 1 to 6 same or different substituents selected from the above-mentioned group of substituents (excluding phenyl group). R ¹¹ , R ¹² , R ¹³ ,
R ¹⁴ and R ¹⁵ are preferably phenoxy groups.

The "aralkyl group" means that the aryl moiety is a phenyl group.
It is a nyl group and the alkyl part has 1 to 6 carbon atoms (preferably
1 to 4) straight-chain or branched-chain alkyl groups.
An arylalkyl group such as a benzyl group,
Phenylpropyl, phenylbutyl or phenyl
A xyl group and the like. The phenyl group is a haloalkyl group
("C above_1-6Similar to "haloalkyl group" can be mentioned.
A halogen atom (as defined above), C_1-6Al
Kill group (as defined above), C_1-6Alkoxy group (as above
Synonyms), C_2-7Alkoxycarbonyl group (same as above
Meaning), nitro group, cyano group, carboxyl group, hydroxyl group,
Amino group, C_1-6Alkylamino group (as defined above) and
C_1-6Alkylamino group (above "C_2-12Zia
Synonymous with “alkylamino group”)
Alternatively, it may be substituted with a different substituent. R⁶At
Preferred is a benzyl group or a 4-fluorobenzyl group.
R ¹¹, R¹², R^Thirteen, R¹⁴And R¹⁵smell
And preferably a benzyl group or a phenylpropyl group
R²⁰And R²¹Is preferably a benzyl group
Yes, R²⁵And R²⁶Is preferably a benzyl group
And R⁴⁶And R^{46 '}In preferably Benji
It is a ru basis.

"Aralkyloxy group" means an aryl moiety.
Is a phenyl group, and the alkoxy group has 1 to 6 carbon atoms.
(Preferably 1 to 4) straight chain or branched chain alkoxy
An arylalkoxy group, which is
Benzyloxy group, phenylpropoxy group, phenylbut
A xy group or a phenylhexyloxy group and the like. Also said
The phenyl group is a haloalkyl group (the above "C_1-6Halo al
Similar to “kill group”), halogen atom
(Synonymous with the above), C_1-6An alkyl group (as defined above),
C_1-6Alkoxy group (as defined above), C_2-7Arco
Xycarbonyl group (as defined above), nitro group, cyano
Group, carboxyl group, hydroxyl group, amino group, C _1-6Al
Kiramino group (as defined above) and di-C_1-6Alkyla
Mino group (above "C_2-12Same as "dialkylamino group"
1 to 6 identical or different substituents selected from
It may be replaced. R^ThreeIn preferably Benji
It is a ruoxy group.

The "acylamino group" has 2 to 13 carbon atoms.
The number of carbon atoms is preferably 2 to 11, and the number of carbon atoms is 2 to 7, for example.
And alkylcarbonylamino (eg, acetylamino, propionylamino, butyrylamino, pivaloylamino, etc.) and the like, and acetylamino is preferable.

The "C _2-7 haloalkylcarbonylamino group" is a haloalkylcarbonylamino group having a preferable carbon number of 2 to 5, in which the haloalkyl moiety has the same meaning as the above "C _1-6 haloalkyl group". Preferred is trifluoromethylcarbonylamino.

The "heteroaryl group" is a heteroaryl group having one or more, preferably 1 to 3, hetero atoms such as nitrogen atom, sulfur atom and oxygen atom, and preferably 4 to 7 membered ring. , And more preferably a 5- or 6-membered ring.
Specifically, thienyl, furyl, imidazolyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, thioxazolyl, diazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepinyl, azepinyl, azepiolinyl. Examples include nil and the like. Pyridyl preferably in R ^{3 8,} R
Thienyl is preferred at ⁴⁶ and ^{46 '} . R ³
The thiazolyl group in may be substituted with a C _1-6 alkyl group (as defined above) or an amino group.

The aralkyl group for R ⁶ may be substituted with a halogen atom (as defined above). The triazolyl group includes both 1,2,3-form and 1,2,4-form. The positions of the bonds of the tetrazolyl group and the triazolyl group are not particularly limited as long as they are possible positions.

"Pharmaceutically acceptable salt" means, for example, various inorganic acid addition salts such as hydrochloride, hydrobromide, sulfate, phosphate or nitrate; acetate, propionate, succinate. , Glycolate, lactate, malate, oxalate, tartrate, citrate, maleate, fumarate, methanesulfonate, benzenesulfonate, p-
Various organic acid addition salts such as toluene sulfonate or ascorbate; salts with various amino acids such as aspartate or glutamate are included, and hydrochloride, methane sulfonate, benzene sulfonate, p-toluene Sulfonates are preferred, and p-toluenesulfonate is particularly preferred. Further, depending on the case, it may be a hydrate, a hydrate or a solvate.

In a preferred embodiment of the compound (1) of the present invention, R ⁶ is, for example, hydrogen atom, C _1-6 alkyl group or aralkyl group (the aralkyl group may be substituted with a halogen atom). R ⁷ is

[Chemical 42] {Where X is = O, = S or = NH; A is
—N (R ^{8 ′} ) — (wherein R ^{8 ′} is a hydrogen atom, C
_1-6 alkyl group or a phenyl group which may have a substituent), -C (R9 ^' ) (R10 ^' )-(wherein R9 ^' and R10 ^' are the same or different) , Hydrogen atom, hydroxyl group, amino group, C _1-6 alkyl group, C _1-6
A hydroxyalkyl group, a C _2-7 alkoxycarbonylamino group or an acylamino group, or R ^{9 ′}
And R ^{10 ′} together with the adjacent carbon atom, C
_3-7 cycloalkyl group may be formed),-(CH
₂ ) _m- NH- (where m is an integer of 1 to 4),
-CO-, -S- or a single bond; B is

[Chemical 43] ^{(Wherein, R 11 ', R 12'} , R 13 ', R 14' or ^{R 15 'are} the same or different, a hydrogen atom, a halogen _{atom, C 1-6 alkyl, C 1-6} alkoxy group, Nitro group, hydroxyl group, cyano group, haloalkyl group, aralkyl group, optionally substituted phenyl group, aryloxy group, tetrazolyl group, triazolyl group,-(CH
₂ ) _p- CO-R19 ^' (here, p is 0 or an integer of 1 to 4, R19 ^' is a phenyl group which may have a substituent, a hydroxyl group, a _C1-6 alkoxy group or -N (R
²⁰ ) (R ²¹ )-(wherein R ²⁰ and R ²¹ are the same as defined in the compound (1) of the present invention),
^{_{-O- (CH 2) r -R 23}} ( where, r and ^{R 23}
Is the same as the definition in the compound (1) of the present invention),
O—CO—R ²⁷ (wherein R ²⁷ has the same definition as in the compound (1) of the present invention), or —N (R
^{28 '} ) (R ^29' ) (wherein R ^{28 '} and R ^29'
Are the same or different, and are each a hydrogen atom, a C _1-6 alkyl group, an optionally substituted phenyl group, an acyl group,
_{- (CH 2) p '-COO} -R 30' ( where, p 'is the same as defined in the present invention compounds (1), R
^{30 ′} is a hydrogen atom, a phenyl group which may have a substituent or a C _1-6 alkyl group (the C _1-6 alkyl group is
A hydroxyl group, a trifluoromethyl group, a phenyl group which may have a substituent, a morpholino group or a carboxyl group)), -CON (R ^{31 ''} )
(R ^{32 ″} ) (where R ^{31 ″} and R
^{32 ″} are the same or different and each is a hydrogen atom, a C _1-6 alkyl group or a phenyl group which may have a substituent), —CO—R ^{33 ′} (wherein R ^{33 ′} is C _1-6
Have an alkyl group or a substituent is also a phenyl group) or _{-CO- (CH 2) r '-R} 34 ( where
r ′ and R ³⁴ are the same as defined in the compound (1) of the present invention), and R ^{16b ′ to} R ^{16n ′.}
And R ^{17b ′ to} R ^{17n ′} are the same or different and each represent a hydrogen atom, a halogen atom, a C _1-6 alkyl group, an amino group,
Hydroxyl group, C _1-6 alkoxy group or -CON (R
^{31 '''} ) (R ^32''' ) (where R ^{31 '''}
And R ^{32 ′ ″} is the same as R ^{31 ″} and R ^{32 ″} ), and R ¹⁸ , Y and n are the same as the definition in the compound (1) of the present invention). ,
Or R ^{6 ′} and R ^{7 ′} together with the adjacent nitrogen atom

[Chemical 44] {Wherein R ³⁶ and R ³⁷ are the same as defined in the compound (1) of the present invention; Z ′ is —CH ₂ —CH ₂ —;
-C ( ^R42 ) = CH-, -C ( ^{R42 '} ) = N-,-
N = N -, - CO - , - CO-O -, - CO-CH 2 -
_{O -, - CH 2 -CO-} NH -, - C (R 42 '')
^{(R 43) -N (R 44} ) - ( ^{wherein, R 4 2, R
42 ′} , R ^{42 ″} and R ⁴³ are the same or different and each is a hydrogen atom, a C _1-6 alkyl group or a phenyl group which may have a substituent, and R ⁴⁴ is the same as in the compound (1) of the present invention. Same as definition) or -C (U) -N (R
^{44 ′} )-(wherein U and R ^{44 ′} are the same as defined in the compound (1) of the present invention); R
^{38 '} is a hydrogen atom, a halogen atom or C
_A phenyl group or a pyridyl group optionally substituted with a _1-6 alkyl group; R ^{39 ′} and R ^{40 ′} are both hydrogen atoms, or R ^{39 ′} and R ^{40 ′} are the same as the adjacent carbon atom; become,

[Chemical formula 45] May be formed; W and V₁Is the compound of the present invention (1)
Is the same as the definition in_Two'Is -O-, -CH_Two
-Or-N (R⁴⁵)-(Where R⁴⁵Is the hydrogen source
Child, C_1-6Alkyl group, substituted with halogen atom
Optionally a phenyl group); V_Three'Is -CH
(R⁴⁶)-Or -N (R^{46 '})-(Where R⁴⁶
And R ^{46 '}Are hydrogen atom, benzyl group,
Phenyl group, halogen atom, hydroxy group or C
_1-6Phenyl group which may be substituted with alkoxy group
Is) may be formed].
And R⁶Is a hydrogen atom, C_1-6Alkyl group or aralkyl
Group (the aralkyl group may be substituted with a halogen atom)
Good); R⁷But,

[Chemical formula 46] {Where X is the same as the definition in the compound (1) of the present invention; A is -N (R ^{8 ''} )-(wherein R ^{8 ''}
Is a hydrogen atom, a C _1-6 alkyl group or an aryl group which may have a substituent), —C (R ^{9 ″} ) (R
^{10 ″} )-(wherein R ^{9 ″} and R ^{10 ″} are the same or different and each represents a hydrogen atom, a hydroxyl group, an amino group, C _1-6.
Alkyl group, C _1-6 hydroxyalkyl group or C _2
-7 alkoxycarbonylamino group, or R ^{9 ″} and R ^{10 ″} may form a C _3-7 cycloalkyl group together with the adjacent carbon atom),
- _{(CH 2)} m -NH- _(where, m is the same as defined in the present invention compound (1)), - CO- or a single bond; B is

[Chemical 47] (Where R ^{11 ″} , R ^{12 ″} , R ^{13 ″} , R
^{14 ″} or R ^{15 ″} are the same or different and each is a hydrogen atom, a halogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group, a nitro group, a hydroxyl group, a cyano group, a haloalkyl group, an aralkyl group or a substituent. aryl group which may have a group, an aryloxy group, a tetrazolyl group, a triazolyl _group, - _(CH 2) at p ^{-CO-R 19} (wherein, p and ^{R 19} are as defined in the present invention compounds (1) is the _{same), - O- (CH 2)} r -R 23 ( where, r and ^{R 23} are present compound (1) as defined ^{in), - O-CO-R} 27 ( wherein, R ²⁷ has the same definition as in the compound (1) of the present invention) or —N (R
^{28 ″} ) (R ^{29 ″} ) (wherein R ^{28 ″} and R ^{28 ″} )
^{29 ″} are the same or different and each is a hydrogen atom, a C _1-6 alkyl group, an aryl group which may have a substituent,
_{(CH 2) p '-COO-} R 30''( wherein, p' is synonymous with ^{p, R 30 ''} is a hydrogen atom or a _{C 1-6} alkyl group (the _{C 1-6} alkyl group, It may be substituted with a hydroxyl group, a trifluoromethyl group or a carboxyl group)
, -CON (R ³¹ ) (R ³² ) (wherein R
³¹ and R ³² are the same as the definition in the compound (1) of the present invention), —CO—R ³³ (wherein R ³³ is the same as the definition in the compound (1) of the present invention) or —CO—.
(CH ₂ ) _r′- R ³⁴ (where r ′ and R ³⁴ are the same as defined in the compound (1) of the present invention), and R ^{16b to} R ¹⁶ⁿ and R ^{17b to} R
¹⁷ⁿ has the same definition as in the compound (1) of the present invention, R ¹⁸ has the same definition as in the compound (1) of the present invention, and Y ″ represents —S— or —N (R ³⁵ ) — (wherein
R ³⁵ is the same as the definition in the compound (1) of the present invention), and n is the same as the definition in the compound (1) of the present invention}, or R ⁶ and R ⁷ are adjacent nitrogen atoms. Together

[Chemical 48] {Where R^{36 ''}And R^{37 ''}Are the same or different
, Hydrogen atom, halogen atom, C_1-6An alkyl group,
C_1-6Alkoxy group, amino group, hydroxyl group or -OC
OR⁴¹(Where R⁴¹In the compound (1) of the present invention
Z '' is -CH._Two−
CH_Two-, -C (R⁴²) = CH-, -N = N-, -C
O-, -CO-O-, -CO-CH_Two-O-, -CH_Two
-CO-NH-, -C (R ^{42 ''}) (R⁴³) -N
(R^{44 ''})-(Where R⁴², R^{42 ''}And R
⁴³Is the same as the definition in the compound (1) of the present invention,
R^{44 ''}Is a hydrogen atom, C_1-6Alkyl group or C
_2-7Is an alkoxycarbonyl group) or -C (U)
-N (R^{44 '''})-(Where U is = O or = S
Yes, R^{44 '' '}Is R^{44 ''}Synonymous with) Yes;
R^{38 ''}May have a hydrogen atom or a substituent
An aryl group; R^{39 ''}And R^{40 ''}Are the same
Or, differently, a hydrogen atom, C_1-6Alkyl group or C
_2-7An alkoxycarbonyl group or R
^{39 ''}And R^{40 ''}Together with the adjacent carbon atom
I mean

[Chemical 49] W ″ is —CO— or —CH ₂ —; V ₁ and V ₂ are the same as defined in the compound (1) of the present invention; and V ₃ is —CH (R ^{46 ′. '} ) -Or-
N (R ^{46 '''} )-(wherein R ^{46' '} and R
^{46 ″ ′} are the same or different and each is a hydrogen atom or an aryl group which may have a substituent). Next, the various substituents or substitution positions will be described in more detail below. R ¹ is preferably a hydrogen atom. R ²
In, a hydrogen atom is preferable. R ³ is preferably a C _1-6 alkyl group or a halogen atom, and particularly preferably a chlorine atom. R ⁴ is preferably a hydrogen atom. R ⁵ is preferably a hydrogen atom. In R ⁷ , preferably, X is ═O or —NH, A is a single bond, and B is

[Chemical 50] (In the formula, each symbol has the same meaning as described above). R ⁶ is preferably a hydrogen atom, or R ⁶ and R ⁷ together with the adjacent nitrogen atom,

[Chemical 51] (Wherein each symbol has the same meaning as described above).

Specific preferred examples of the compound (1) of the present invention are shown below.
Listed in: Benzoic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide, 2-aminobenzoyl
Aromatic acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 2-hydroxybenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 3- (2- (2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazinocarbonyl) fe
Nylcarbamoyloxy) -2,2-dimethylpropio
Acid, benzoic acid 2- (5-chloro-1H-indole
-2-Carbonyl) -1-methylhydrazide, benzoic acid
2- (1-acetyl-5-chloro-1H-indole
-2-carbonyl) hydrazide, 5-chloro-1H-i
Ndol-2-carboxylic acid 2- (imino-phenyl-)
Methyl) hydrazide, 5-aminothiazole-4-cal
Boronic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, benzoic acid 2- (5-fluoro)
-1H-indole-2-carbonyl) hydrazide, shi
Chlorohexanecarboxylic acid 2- (5-fluoro-1H-
Indole-2-carbonyl) hydrazide, thiophene
-2-carboxylic acid 2- (5-fluoro-1H-indo)
2-carbonyl) hydrazide, 4-nitrobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 2-methylbenzoic acid 2- (5-ku)
Lolo-1H-indole-2-carbonyl) hydrazide
De, 4-methylbenzoic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, 2-methoxy
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 3-methoxybenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 4-methoxybenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 3-
Methylbenzoic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide, 2-chlorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
) Hydrazide, 3-chlorobenzoic acid 2- (5-chloro)
-1H-indole-2-carbonyl) hydrazide,
4-chlorobenzoic acid 2- (5-chloro-1H-indo
2-carbonyl) hydrazide, 4- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) benzoic acid methyl ester, cyclohexa
Carboxylic acid 2- (5-chloro-1H-indole-
2-Carbonyl) hydrazide, 2,4-dichlorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nil) hydrazide, 2,6-dichlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2,4-difluorobenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
De, biphenyl-2-carboxylic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 3-
Fluorobenzoic acid 2- (5-chloro-1H-indole
-2-carbonyl) hydrazide, 4-fluorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 3-trifluoromethylbenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 4-trifluoromethylbenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-trifluoromethylbenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, benzoic acid 2- (5-methyl-1H-indo)
2-carbonyl) hydrazide, benzoic acid 2-
(5-chloro-3-methyl-1H-indole-2-ca
Lubonyl) hydrazide, benzoic acid 2- (5,7-dicu
Lolo-1H-indole-2-carbonyl) hydrazide
2-aminobenzoic acid 2- (5-isopropyl-1)
H-indole-2-carbonyl) hydrazide, 2-a
Mino-4-fluorobenzoic acid 2- (5-isopropyl)
-1H-indole-2-carbonyl) hydrazide, 2
-Aminobenzoic acid 2- (5-fluoro-1H-indo)
2-carbonyl) hydrazide, 2-aminobenzoic acid
Acid 2- (6-chloro-1H-indole-2-carb
Nyl) hydrazide, 3-amino-4- (2- (5-chloro)
B-1H-indole-2-carbonyl) hydrazinoca
Lubonyl) benzoic acid methyl ester, 3-aminoisononi
Cotinic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, isonicotinic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
De, nicotinic acid 2- (5-chloro-1H-indole
-2-carbonyl) hydrazide, pyridine-2-carbo
Acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 3- (dimethylamino) benzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, N- (3- (2- (5-chloro-1H
-Indole-2-carbonyl) hydrazinocarboni
L) phenyl) acetamide, N- (2- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) phenyl) acetamide, 4-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) -2-methylhydrazide, 2- (2- (2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazinocarbonyl) phenoxy) acetic acid methyl ester
2-, 2- (2- (2- (5-chloro-1H-indole
L-2-carbonyl) hydrazinocarbonyl) phenoki
Si) acetic acid, 2- (dimethylamino) benzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 2- (2- (5-chloro-1H-indole
-2-Carbonyl) hydrazinocarbonyl) phenoxy
-N, N-dimethylacetamide, 2-methylamino ammonium
Benzoic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 2-amino-4-chlorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 2-amino-6-chlorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-amino-3-chlorobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-amino-5-chlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 4-cyanobenzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 4-
(1H-tetrazol-5-yl) benzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 3- (1H-tetrazol-5-yl) benzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2- (2- (2- (5-chloro-1H
-Indole-2-carbonyl) hydrazinocarboni
Le) anilino) acetic acid, 2-aminobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide
2-amino-4-fluorobenzoic acid 2- (5-me
Chill-1H-indole-2-carbonyl) hydrazide
Demethyl, 2- (2- (5-methyl-1H-indole)
L-2-carbonyl) hydrazinocarbonyl) pheny
Carbamate, 2- (2- (5-chloro-1H-i)
Ndol-2-carbonyl) hydrazinocarbonyl)
Phenyl dimethyl carbamate, 2-aminobenzoic acid
2- (5-ethyl-1H-indole-2-carboni
Le) hydrazide, 2-amino-4,5-difluorobenzoate
Aromatic acid 2- (5-methyl-1H-indole-2-cal
Bonyl) hydrazide, 2- (2-hydroxyethoxy)
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 2- (3- (2- (5-chloro
B-1H-indole-2-carbonyl) hydrazinoca
Lubonyl) phenoxy) acetic acid methyl ester, 2- (3
-(2- (5-chloro-1H-indole-2-carb
Nil) hydrazinocarbonyl) phenoxy) acetic acid, 2-
(3- (2- (5-chloro-1H-indole-2-car
Rubonyl) hydrazinocarbonyl) phenoxy) -N,
N-dimethylacetamide, 2-methylthiazole-4
-Carboxylic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 4- (2H- [1,2,
4] triazol-3-yl) benzoic acid 2- (5-ku)
Lolo-1H-indole-2-carbonyl) hydrazide
De, 3- (2H- [1,2,4] triazol-3-i
) Benzoic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 1,3-dihydroxy-
2-propyl (2- (2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazinocarbonyl) fe
Nyl) carbamate, 3-((2- (2- (5-chloro
-1H-indole-2-carbonyl) hydrazinocar
Bonyl) phenyl) carbamoyloxy) -2,2-di
Methyl propionic acid, thiophene-2-carboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, furan-2-carboxylic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
2,6-Dichloronicotinic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 1H-pi
Roll-2-carboxylic acid 2- (5-chloro-1H-i)
Ndol-2-carbonyl) hydrazide, 1H-imida
Zol-4-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, pyrazine-2
-Carboxylic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, thiophene-3-carbo
Acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, furan-3-carboxylic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 5-chlorothiophene-2-carboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 3-chlorothiophene-2-carboxylic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 1-methyl-1H-pyrrole-2-ca
Rubonic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 5-methylthiophene-2-
Carboxylic acid 2- (5-chloro-1H-indole-2
-Carbonyl) hydrazide, 3-methylthiophene-2
-Carboxylic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 2,6-difluorobenzoate
Aromatic acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 2,3-difluorobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 5-chloro-1H-indole-2-cal
Boronic acid 2- (naphthalene-1-carbonyl) hydrazide
De 3,4,5-trifluorobenzoic acid 2- (5-
Lolo-1H-indole-2-carbonyl) hydrazide
2,3,4,5-tetrafluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2-amino-4-methylbenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 2-amino-4-fluorobenzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
2-amino-5-methylbenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
2-Amino-6-methylbenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 2-
Amino-3-methylbenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 2-ami
No-4,5-difluorobenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 3-
Aminothiophene-2-carboxylic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide, 2
-Aminobenzoic acid 2- (5-bromo-1H-indole
2-L-carbonyl) hydrazide, 2-amino-4-fluoro
Luorobenzoic acid 2- (5-bromo-1H-indole
-2-Carbonyl) hydrazide, 1H-pyrazole-4
-Carboxylic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, methyl (2- (2-
(5-Fluoro-1H-indole-2-carbonyl)
Hydrazinocarbonyl) phenyl) carbamate, 1-
Methyl-1H-pyrrole-2-carboxylic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide
And thiophene-3-carboxylic acid 2- (5-methyl-
1H-indole-2-carbonyl) hydrazide, 4H
-Thieno [3,2-b] pyrrole-5-carboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, phenyl (2- (2- (5-chloro-1
H-indole-2-carbonyl) hydrazinocarboni
Lu) phenyl) carbamate, benzyl (2- (2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazinocarbonyl) phenyl) carbamate, 2-hi
Droxyethyl (2- (2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazinocarbonyl)
Phenyl) carbamate, 3-hydroxypropyl (2
-(2- (5-chloro-1H-indole-2-carb
Nyl) hydrazinocarbonyl) phenyl) carbame
2-((2- (5-chloro-1H-indole-2
-Carbonyl) hydrazinocarbonyl) phenyl) calc
Vamoyloxy) acetic acid, 2-((2- (2- (5-chloro
B-1H-indole-2-carbonyl) hydrazinoca
Rubonyl) phenyl) carbamoyloxymethyl) -2
-Methylmalonic acid, methyl 2- (2- (5-chloro-
1H-indole-2-carbonyl) hydrazinocarb
Nyl) phenyl carbamate, cyclohexane carvone
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) -1-methylhydrazide, thiophene-2-cal
Boronic acid 2- (5-chloro-1H-indole-2-ca)
Rubonyl) -1-methylhydrazide, benzoic acid 2-
(1H-indole-2-carbonyl) hydrazide, cheap
Benzoic acid 2- (5-chloro-1-methyl-1H-indo)
2-carbonyl) hydrazide, benzoic acid 2-
(5-methoxy-1H-indole-2-carbonyl)
Hydrazide, benzoic acid 2- (5-isopropyl-1H
-Indole-2-carbonyl) hydrazide, benzoic acid
2- (5-nitro-1H-indole-2-carboni
Le) hydrazide, benzoic acid 2- (5-benzyloxy)
-1H-indole-2-carbonyl) hydrazide, cheap
Benzoic acid 2- (6-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 6H-thieno [2,3-b] pi
Roll-5-carboxylic acid 2- (5-chloro-1H-i)
Ndol-2-carbonyl) hydrazide, 5-chloro-
1H-indole-2-carboxylic acid 2-((2-furo
Orophenyl) -imino-methyl) hydrazide, 5-qua
Lolo-1H-indole-2-carboxylic acid 2-((3
-Fluorophenyl) -imino-methyl) hydrazide,
5-chloro-1H-indole-2-carboxylic acid 2-
((4-Fluorophenyl) -imino-methyl) hydra
Zido, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (p-tolyl) -methyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((4-chlorophenyl) -imino-methyl) hydr
Lazide, 5-chloro-1H-indole-2-carvone
Acid 2-((3-chlorophenyl) -imino-methyl)
Hydrazide, 5-chloro-1H-indole-2-cal
Boronic acid 2-((2-chlorophenyl) -imino-methyl
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2- (imino- (o-tolyl) -methyl)
Hydrazide, 5-chloro-1H-indole-2-cal
Boronic acid 2- (imino- (m-tolyl) -methyl) hydr
Lazide, 5-chloro-1H-indole-2-carvone
Acid 2- (imino- (thiophen-2-yl) -methyl
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2- (imino- (pyridin-2-yl)-
Methyl) hydrazide, 5-chloro-1H-indole-
2-carboxylic acid 2-((furan-2-yl) -imino
-Methyl) hydrazide, 5-chloro-1H-indole
-2-carboxylic acid 2-((2-chloro-6-fluoro
Phenyl) -imino-methyl) hydrazide, 5-chloro
-1H-indole-2-carboxylic acid 2- (imino-
(2-Trifluoromethylphenyl) -methyl) hydra
Zido, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (pyrazin-2-yl) -methyl) hi
Dolazide, 3-aminobenzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 3-me
Toxybenzoic acid 2- (5-chloro-1H-indole
-2-carbonyl) hydrazide, 5-amino-2-methyi
Luthiazole-4-carboxylic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 5-ku
Lolo-1H-indole-2-carboxylic acid (1,2,
3,4-tetrahydro-2,4-dioxoquinazoline-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid (2,3-dihydro-2,4-dioxo
-4H-benzo [e] [1,3] oxazin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boronic acid (1,2,3,4-tetrahydro-4-oxo
-2-thioxoquinazolin-3-yl) amide, 5-qua
Lolo-1H-indole-2-carboxylic acid (3,4-
Dihydro-2-methyl-4-oxoquinazolin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (3,4-dihydro-4-oxoquinazoline-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid (1,2,3,4-tetrahydro-4-
Oxoquinazolin-3-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid (1,2,3,4-
Tetrahydro-2,5-dioxo-5H-benzo [e]
[1,4] diazepin-4-yl) amide, 5-chloro
-1H-indole-2-carboxylic acid (2,3,4,
5-Tetrahydro-3,5-dioxo-benzo [f]
[1,4] Oxazepin-4-yl) amide, 5-i
Sopropyl-1H-indole-2-carboxylic acid
(1,2,3,4-tetrahydro-2,4-dioxoki
Nazolin-3-yl) amide, 5-isopropyl-1H
-Indole-2-carboxylic acid (7-fluoro-1,
2,3,4-tetrahydro-2,4-dioxoquinazoli
N-3-yl) amide, 5-fluoro-1H-indole
Le-2-carboxylic acid (1,2,3,4-tetrahydro
-2,4-dioxoquinazolin-3-yl) amide, 6
-Chloro-1H-indole-2-carboxylic acid (1,
2,3,4-tetrahydro-2,4-dioxoquinazoli
N-3-yl) amide, 3-((5-chloro-1H-i
Ndole-2-carbonyl) amino) -1,2,3,4
-Tetrahydro-2,4-dioxoquinazoline-7-ca
Rubonic acid methyl ester, 3-((5-chloro-1H-
Indole-2-carbonyl) amino) -1,2,3
4-Tetrahydro-2,4-dioxoquinazoline-7-
Carboxylic acid, 5-chloro-1H-indole-2-cal
Boronic acid (1,2,3,4-tetrahydro-2,4-di
Oxo-6- (trifluoroacetylamino) quinazoli
N-3-yl) amide, 5-chloro-1H-indole
-2-carboxylic acid (6-amino-1,2,3,4-tetracarboxylic acid
Trahydro-2,4-dioxoquinazolin-3-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (5-chloro-1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-3-yl) amide, 5-
Chloro-1H-indole-2-carboxylic acid (6-
Lolo-1,2,3,4-tetrahydro-2,4-dioki
Soquinazolin-3-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid (7-chloro-1,2,
3,4-tetrahydro-2,4-dioxoquinazoline-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid (8-chloro-1,2,3,4-tetra
Hydro-2,4-dioxoquinazolin-3-yl) ami
2- (3-((5-chloro-1H-indole-2
-Carbonyl) amino) -1,2,3,4-tetrahydr
(2,4-dioxoquinazolin-1-yl) acetic acid, 2
-(3-((5-chloro-1H-indole-2-cal
Bonyl) amino) -1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-1-yl) acetic acid methyl ester
Stell, 5-methyl-1H-indole-2-carvone
Acid (1,2,3,4-tetrahydro-2,4-dioki
Soquinazolin-3-yl) amide, 5-methyl-1H-
Indole-2-carboxylic acid (7-fluoro-1,
2,3,4-tetrahydro-2,4-dioxoquinazoli
N-3-yl) amide, 5-ethyl-1H-indole
-2-carboxylic acid (1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-3-yl) amide, 5-
Methyl-1H-indole-2-carboxylic acid (6,7
-Difluoro-1,2,3,4-tetrahydro-2,4
-Dioxoquinazolin-3-yl) amide, 5-methyl
-1H-indole-2-carboxylic acid (1,2,3,
4-tetrahydro-6-methoxy-2,4-dioxoki
Nazolin-3-yl) amide, 5-methyl-1H-yne
Dole-2-carboxylic acid (1,2,3,4-tetrahydo
Doro-6-hydroxy-2,4-dioxoquinazoline-
3-yl) amide, acetic acid 3-((5-methyl-1H-
Indole-2-carbonyl) amino) -1,2,3
4-Tetrahydro-2,4-dioxoquinazoline-6-
Ile ester, 5-chloro-1H-indole-2-ca
Rubonic acid (1,2,3,4-tetrahydro-2,4-
Dioxo-1-propylquinazolin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(1,2,3,4-tetrahydro-1-methyl-2,4
-Dioxoquinazolin-3-yl) amide, N- (1,
2,3,4-tetrahydro-7-nitro-2,4-dio
Xoxoquinazolin-3-yl) -5-chloro-1H-yne
Dole-2-carboxylic acid amide, 5-chloro-1H-i
Ndole-2-carboxylic acid (2,4-dioxoperch
Doropyrimidin-3-yl) amide, 5-chloro-1H
-Indole-2-carboxylic acid (4-oxo-2-thio)
Oxoperhydropyrimidin-3-yl) amide, 5-
Chloro-1H-indole-2-carboxylic acid (2,4
-Dioxo-1-phenylperhydropyrimidine-3-
Yl) amide, 5-chloro-1H-indole-2-ca
Rubonic acid (4-oxo-1-phenylperhydropyrrole
Midin-3-yl) amide, 5-chloro-1H-indo
2-carboxylic acid (1- (4-fluorophenyl
) -2,4-Dioxoperhydropyrimidin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boronic acid (2,4-dioxo-1- (pyridin-2-i
Le) perhydropyrimidin-3-yl) amide, 5-
Lolo-1H-indole-2-carboxylic acid (1- (3
-Fluorophenyl) -2,4-dioxoperhydropi
Limidin-3-yl) amide, 5-chloro-1H-yne
Dole-2-carboxylic acid (1- (2-fluorophenyl
) -2,4-Dioxoperhydropyrimidin-3-i
Le) amide, 5-fluoro-1H-indole-2-car
Rubonic acid (2,4-dioxo-1-phenyl-perch
Doropyrimidin-3-yl) amide, 5-methyl-1H
-Indole-2-carboxylic acid (2,4-dioxo-
1-phenyl-perhydropyrimidin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(1- (3-chlorophenyl) -2,4-dioxoper
Hydropyrimidin-3-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid (2,4-dioxo
-1- (m-tolyl) perhydropyrimidin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (2,4-dioxo-1- (p-tolyl) per
Hydropyrimidin-3-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid (1- (4-chloro
Phenyl) -2,4-dioxoperhydropyrimidine-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid (2,4-dioxo-1- (o-tri
Le) perhydropyrimidin-3-yl) amide, 5-
Lolo-1H-indole-2-carboxylic acid ((4S)
-2,5-Dioxo-4-phenylimidazolidine-1
-Yl) amide, 5-chloro-1H-indole-2-
Carboxylic acid (2,4-dioxo-1-phenylimidazole
Zolidin-3-yl) amide, 5-chloro-1H-yne
Dole-2-carboxylic acid (4-oxo-1-phenyl
-2-thioxoimidazolidin-3-yl) amide, 5
-Chloro-1H-indole-2-carboxylic acid (4-
Oxo-1-phenylimidazolidin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(2-oxo-1-phenylimidazolidin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid ((4R) -2,5-dioxo-4-phenyl
Imidazolidin-1-yl) amide, 5-chloro-1H
-Indole-2-carboxylic acid ((4S) -1,3-
Dioxo-perhydropyrrolo [1,2-c] imidazo
Lu-2-yl) amide, 5-chloro-1H-indole
2-carboxylic acid ((4R) -1,3-dioxo-para
-Hydropyrrolo [1,2-c] imidazol-2-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid ((4S) -4-benzyl-2,5-dioxo
Imidazolidin-1-yl) amide, 5-chloro-1H
-Indole-2-carboxylic acid ((4R) -4-ben
Zil-2,5-dioxoimidazolidin-1-yl) a
Mido, 5-chloro-1H-indole-2-carboxylic acid
(2,4-dioxoimidazolidin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(1-Methyl-2,5-dioxo-4-phenylimidazole
Zolidin-1-yl) amide, 5-chloro-1H-yne
Dole-2-carboxylic acid (2,4-dioxo-1-
(4-Fluorophenyl) imidazolidin-3-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (2,5-dioxo-4- (2-fluorophenyl)
Ru) imidazolidin-1-yl) amide, 5-chloro-
1H-indole-2-carboxylic acid (2,5-dioxy
So-4- (2-thienyl) imidazolidin-1-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (2,5-dioxo-4- (4-fluorophenyl)
Ru) imidazolidin-1-yl) amide, 5-chloro-
1H-indole-2-carboxylic acid (2,5-dioxy
So-4- (4-chlorophenyl) imidazolidine-1-
Yl) amide, 5-chloro-1H-indole-2-ca
Rubonic acid ((4S) -2,5-dioxo-4- (4-
Hydroxyphenyl) imidazolidin-1-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
((4S) -2,5-dioxo-4- (4-methoxyphenyl)
Phenyl) imidazolidin-1-yl) amide, 5-chloro
B-1H-indole-2-carboxylic acid ((4R)-
2,5-dioxo-4- (4-methoxyphenyl) imi
Dazolidin-1-yl) amide, 5-chloro-1H-i
Ndole-2-carboxylic acid 2- (anilinocarboni
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2- (phenylthiocarbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2- (2-phenylacetyl) hydrazide, 5-chloro
-1H-indole-2-carboxylic acid 2- (2-oxy
So-2-phenylacetyl) hydrazide, 5-chloro-
1H-indole-2-carboxylic acid 2-((2-full
Orophenyl) aminocarbonyl) hydrazide, 5-chloro
Lolo-1H-indole-2-carboxylic acid 2-((3
-Fluorophenyl) aminocarbonyl) hydrazide,
5-chloro-1H-indole-2-carboxylic acid 2-
((4-Fluorophenyl) aminocarbonyl) hydra
Zido, 5-chloro-1H-indole-2-carboxylic acid
2- (anilinocarbonyl) -2-methylhydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((2-chloroanilino) carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((3-chloroanilino) carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((4-chloroanilino) carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((1-phenylcyclopropane) carbonyl) hi
Dorazide, 5-chloro-1H-indole-2-carb
2-((1-phenylcyclopentane) carbonic acid
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2-((1-phenylcyclohexane) ca
Lubonyl) hydrazide, 5-chloro-1H-indole
-2-carboxylic acid 2- (2-phenylpropanoyl)
Hydrazide, 5-chloro-1H-indole-2-cal
Boronic acid 2- (3-hydroxy-2-phenylpropano)
Il) hydrazide, 5-chloro-1H-indole-2
-Carboxylic acid 2- (2-methyl-2-phenylpropa
Noyl) hydrazide, 5-chloro-1H-indole-
2-carboxylic acid 2-((2S) -2-amino-2-fur
Phenylacetyl) hydrazide, N- (2- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
No) -2-oxo-1-phenylethyl) acetami
2-morpholinoethyl (2-((2- (5-chloro
B-1H-indole-2-carbonyl) hydrazino)
Carbonyl) phenyl) carbamate p-toluene
Ruphonate, 2-amino-4,5-difluorobenzoic acid
2- (5-methyl-1H-indole-2-carboni
Le) hydrazide benzene sulfonate, 2-amino-
4-Fluorobenzoic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide benzenesulfo
Phosphate, 3-dimethylaminobenzoic acid 2- (5-chloro
B-1H-indole-2-carbonyl) hydrazide
Methanesulfonate, 2-amino-4-fluorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide hydrochloride, 2-amino-4-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide p-toluenesulfonate,
2-Amino-4-fluorobenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide p
-Toluene sulfonate, 2-amino-4-fluoro ammonium
Benzoic acid 2- (5-chloro-1H-indole-2-ca)
Rubonyl) hydrazide p-toluenesulfonate, 2
-Amino-4-fluorobenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide p-
Toluenesulfonate, 2-aminobenzoic acid 2- (5
-Methyl-1H-indole-2-carbonyl) hydra
Zido p-toluenesulfonate, 2-aminobenzoic acid
2- (5-methyl-1H-indole-2-carboni
Le) hydrazide benzene sulfonate, 2-amino-
4-Fluorobenzoic acid 2- (5-methyl-1H-yne
Dole-2-carbonyl) hydrazide benzenesulfo
Phosphate, 3-aminobenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide p-tolu
Ensulfonate, 5-chloro-1H-indole-2
-Carboxylic acid 2-((2-chlorophenyl) -imino
-Methyl) hydrazide methanesulfonate, 5-chloro
B-1H-indole-2-carboxylic acid 2-((2-
Chlorophenyl) -imino-methyl) hydrazide p-
Toluene sulfonate, 5-chloro-1H-indole
-2-carboxylic acid 2-((2-chlorophenyl) -i
Mino-methyl) hydrazide hydrochloride, 5-chloro-1H
-Indole-2-carboxylic acid 2- (imino-phenyl
L-methyl) hydrazide methanesulfonate, 5-chloro
Lolo-1H-indole-2-carboxylic acid 2-((2
-Chlorophenyl) -imino-methyl) hydrazide
Tendioate, 5-chloro-1H-indole-2-cal
Boronic acid 2-((2-fluorophenyl) -imino-me
Chill) hydrazide hydrochloride, 5-chloro-1H-indo
2-carboxylic acid 2-((2-fluorophenyl
) -Imino-methyl) hydrazide methanesulfonic acid
Salt, 5-chloro-1H-indole-2-carboxylic acid
2-((1-imino-2-phenylethyl) hydrazide
Methanesulfonate, 5-chloro-1H-indole
-2-carboxylic acid 2-((3-fluorophenyl)-
Imino-methyl) hydrazide hydrochloride, 5-chloro-1
H-indole-2-carboxylic acid 2-((3,4-di
Fluorophenyl) -imino-methyl) hydrazide
Tansulphonate, 5-chloro-1H-indole-2
-Carboxylic acid 2- (imino- (2-methoxyphenyl
) -Methyl) hydrazide methanesulfonate, 5-
Chloro-1H-indole-2-carboxylic acid 2-
((2,6-difluorophenyl) -imino-methyl)
Hydrazide methanesulfonate, 5-chloro-1H-
Indole-2-carboxylic acid 2-((2,4-diflu
Orophenyl) -imino-methyl) hydrazide methane
Sulfonate, 5-chloro-1H-indole-2-ca
Rubonic acid 2-((1,2-dimethyl-1H-pyrrole
-5-yl) -imino-methyl) hydrazide methan
Ruphonate, 2-aminobenzoic acid 2- (5-methyl-)
1H-indole-2-carbonyl) hydrazide p-
Toluenesulfonate, 2-aminobenzoic acid 2- (5
-Methyl-1H-indole-2-carbonyl) hydra
Zido benzene sulfonate, 2-amino-4-fluor
B-benzoic acid 2- (5-methyl-1H-indole-2)
-Carbonyl) hydrazide benzene sulfonate, 2
-Dimethylaminobenzoic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide p-tolue
Sulfonate, 2-amino-4-fluorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide methanesulfonate, 2-aminobenzoate
Aromatic acid 2- (5-bromo-1H-indole-2-cal
Bonyl) hydrazide methanesulfonate, 2-amino
-4-Fluorobenzoic acid 2- (5-methyl-1H-i)
Ndol-2-carbonyl) hydrazide p-toluene
Sulfonate and 2-amino-4-fluorobenzoic acid
Acid 2- (5-methyl-1H-indole-2-carbo
Nil) hydrazide methanesulfonate.

The numbers on the left end correspond to the embodiment numbers (note that 1-1, 2-1, 3-1, 4-1, 5-1 and 6-1 are the embodiments 1, 2, 3 respectively). 4, 5, and 6
Equivalent to). Among these, more preferable specific examples include the above 1-1 to 1-143 and 6-1 to 6-3.
Compounds listed in 5, more preferably 6 above.
It is a compound mentioned in -1 to 6-35.

The compound (1) of the present invention may be used in some cases.
May be a hydrate or solvate, and
Drugs and metabolites are also included.
The "prodrug" in the present invention means chemical or metabolic
It has a group that can be decomposed dynamically, and
Or by decomposing under physiological conditions
It is a derivative of the compound (1) of the present invention showing activity. example
For example, with respect to the hydroxyl group of the compound, -CO-alkyl, -C
O₂-Alkyl, -CONH-alkyl, -CO-ar
Kenyl, -CO₂-Alkenyl, -CONH-alkeni
-CO, aryl, -CO₂-Aryl, -CON
H-aryl, -CO-heterocycle, -CO₂-Heterocycle,-
CONH-heterocycle (the alkyl, alkenyl, aryl
And heterocycles are halogen atoms, alkyl groups, hydroxyl groups,
Coxy group, carboxy group, amino group, amino acid residue,-
PO₃H₂, -SO₃H, -OPO₃H₂, -OSO₃With H etc.
It may be replaced. ), -CO- polyethylene glycol
Residue, -CO₂-Polyethylene glycol residue, -C
O-polyethylene glycol monoalkyl ether residue
Group, -CO₂-Polyethylene glycol monoalkyl ether
Ether residue or -PO₃H₂Or the like, or compounds
To the amino group of -CO-alkyl, -CO₂-A
Rutile, -CO-alkenyl, -CO₂-Alkenyl,
-CO₂-Aryl, -CO-aryl, -CO-hetero
Ring, -CO₂A heterocycle (wherein the alkyl, alkenyl, ari
And heterocycles are halogen atoms, alkyl groups, hydroxyl groups,
Alkoxy group, carboxy group, amino group, amino acid residue
Group, -PO₃H₂, -SO₃H, -OPO₃H₂, -OSO₃
It may be substituted with H or the like. ), -CO-polyethylene
Recall residue, -CO₂-Polyethylene glycol residue
Group, -CO-polyethylene glycol monoalkyl ether
Tell residue, -CO₂-Polyethylene glycol mono
Killether residue or -PO₃H₂Replaced by etc.
Or a carboxy group of the compound, an alkoxy group,
Aryloxy group (the alkoxy group, aryloxy group
Is a halogen atom, alkyl group, hydroxyl group, alkoxy group,
Carboxy group, amino group, amino acid residue, -PO₃H₂,
-SO₃H, -OPO₃H ₂, -OSO₃Replaced by H etc.
Good. ), Polyethylene glycol residue or polyethylene
The lenglycol monoalkyl ether residue was replaced
I can list things.

When the present invention is used as a therapeutic drug for diabetes, it is administered systemically or locally, orally or parenterally. The dose varies depending on age, weight, symptoms, therapeutic effect, etc., but is usually 10 mg to 1 g per adult per dose.
In the range of 1 to several times daily.

The compound (1) of the present invention is a solid or liquid composition for oral administration, or a diluent, dispersant, or the like suitable for preparing a preparation such as an injection for parenteral administration.
An adsorbent, a dissolving agent, etc. can be mixed.

The compound (1) of the present invention can be used not only for humans but also for the treatment and prevention of diabetes in non-human animals such as mammals.

The compound (1) of the present invention can be used in combination with one drug or a plurality of other drugs by a general method generally used for medicines. Although there are various drugs that can be used in combination with the compound (1) of the present invention, a drug for treating hyperlipidemia and a drug for treating diabetes are particularly preferable.

Examples of the hyperlipidemia remedies that can be used in combination include statin drugs, specifically, lovastatin,
Examples include simvastatin, pravastatin, fluvastatin, atorvastatin, cerivastatin and the like. Similarly, the therapeutic drugs for diabetes that can be used in combination include insulin preparations, sulfonylureas, insulin secretagogues, sulfonamides, biguanides, α-glucosidase inhibitors, insulin sensitizers, and the like. Specific examples are as follows. For example, insulin as insulin preparation, sulfonylurea drug as glibenclamide, tolbutamide, gliclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, etc. Examples of α-glucosidase inhibitors such as metformin and buformin hydrochloride include voglibose and acarbose, and examples of insulin sensitizers include pioglitazone hydrochloride.

Further, the present inventors synergistically exert a therapeutic and preventive effect on diabetes by using an HLGPa inhibitor which has not been used in combination with an antidiabetic agent so far, as compared with the case of using each agent alone. I found that I can. That is, the combined use of the compound (1) of the present invention with a therapeutic drug for diabetes is useful in terms of effects.

Next, an example of a method for producing the indole compound represented by the compound (1) will be described, but the production method of the present invention is not limited to this. Further, when carrying out the reaction described below, functional groups other than the site may be protected in advance, if necessary, and deprotected at an appropriate stage. The amount of the solvent used in each step is not particularly limited as long as the reaction mixture can be stirred. Also,
As the reagent used in each step, a hydrate or salt thereof can be used as long as it does not inhibit the intended reaction. Further, in each step, the reaction may be carried out by a commonly used method, and isolation and purification may be carried out by appropriately selecting or combining commonly used methods such as crystallization, recrystallization, column chromatography and preparative HPLC. I'll do it.

Production Method 1 In the compound represented by the general formula (1), R ⁷ is —C (═O).
-Ring D or -C (= NH) -Ring D (wherein, Ring D is represented by the formula (a)
To (s) is a group selected from the groups represented by (s)), the production method is illustrated below.

[Chemical 52]

(Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵
Is as defined above, R ^{6 ′} is a hydrogen atom, a C _1-6 alkyl group or an aralkyl group (the aralkyl group may be substituted with a halogen atom), X ₁ is a halogen atom, X ₂ is a halogen atom or a hydroxyl group, and ring D
Is a group selected from the groups represented by formulas (a) to (s). )

Step 1-1 By reacting the compound represented by the general formula (2) with the compound represented by the general formula (3) in a solvent in the presence of a base, the compound represented by the general formula (4) is represented. Can be obtained. Examples of the base used in the reaction include alkali metal hydrides such as sodium hydride and potassium hydride; sodium ethoxide, sodium methoxide, potassium t
alk-alkoxides such as ert-butoxide; n
-Alkyllithium such as butyllithium and sec-butyllithium; alkali metal azides such as lithium diisopropylamide, sodium amide and lithium bistrimethylsilylazide; alkali metal carbonates such as sodium carbonate and potassium carbonate; sodium hydrogencarbonate, potassium hydrogencarbonate, etc. Alkali metal hydrogen carbonate of lithium; lithium hydroxide,
Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; Carboxylic acid alkali metal salts such as sodium acetate and potassium acetate; Phosphorus alkali metal salts such as sodium phosphate and potassium phosphate; Triethylamine, pyridine, N-methyl Examples thereof include organic bases such as morpholine, and sodium hydride is preferable. Examples of the solvent include diethyl ether and tetrahydrofuran (TH
F), ether solvents such as dioxane, 1,2-dimethoxyethane and diglyme; hydrocarbon solvents such as benzene, toluene, hexane and xylene; halogen solvents such as dichloromethane, chloroform, carbon tetrachloride and 1,2-dichloroethane Solvents; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol; ester solvents such as ethyl acetate, methyl acetate, butyl acetate; acetone, N, N-dimethylformamide,
Examples thereof include polar solvents such as dimethyl sulfoxide, and these can be used alone or in combination. The preferred solvent in this reaction is N, N-dimethylformamide.
The reaction temperature is generally -50 ° C to 50 ° C, preferably -20
C to room temperature. The reaction time is usually 1 to 10 hours,
It is preferably 1 hour to 5 hours, more preferably 2 hours to
5 hours.

Step 1-2 By reacting the compound represented by the general formula (4) with the compound represented by the general formula (5) in a solvent in the presence of a condensing agent, the compound represented by the general formula (6) is represented. The compound can be obtained. Examples of the solvent include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, and diglyme; hydrocarbon solvents such as benzene, toluene, hexane, and xylene; dichloromethane, chloroform, carbon tetrachloride, and 1 , 2-dichloroethane and other halogen-based solvents; methanol, ethanol,
Examples thereof include alcohol solvents such as isopropyl alcohol and tert-butanol; ester solvents such as ethyl acetate, methyl acetate and butyl acetate; polar solvents such as acetone, N, N-dimethylformamide, and dimethyl sulfoxide; Can be used together. The preferred solvent in this reaction is N, N-dimethylformamide. The condensing agent may be a condensing agent used in a usual peptide condensation method (for example, an acid chloride method, a mixed acid anhydride method, etc.), and among them, 1-hydroxybenzotriazole monohydrate and 1- (3 A combination with-(dimethylamino) propyl) -3-ethylcarbodiimide hydrochloride is preferred. The reaction temperature is usually -20 ° C to 50 ° C,
The temperature is preferably 0 ° C to room temperature. The reaction time is usually 1 hour
It is 48 hours, preferably 2 hours to 24 hours.

Step 1-3 As a target compound, a compound represented by the general formula (6) is reacted with a compound represented by the general formula (7) in a solvent using a condensing agent or a base. Certain general formula (1-2)
A compound represented by can be obtained. A base can be used to smoothly carry out this reaction. For example, in the general formula (7), when X ₂ is a hydroxyl group, a condensing agent is used, and a base may be further used in order to perform smoothly. Further, when X ₂ is a halogen atom, the reaction can be smoothly carried out by using a base without using a condensing agent. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and diglyme; hydrocarbon solvents such as benzene, toluene, hexane and xylene; dichloromethane, chloroform and tetrachloride. Halogen-based solvents such as carbon and 1,2-dichloroethane; alcohol-based solvents such as methanol, ethanol, isopropyl alcohol and tert-butanol; ester-based solvents such as ethyl acetate, methyl acetate and butyl acetate;
Examples thereof include polar solvents such as acetone, N, N-dimethylformamide, and dimethyl sulfoxide, and these can be used alone or in combination. The preferred solvent in this reaction is N, N-dimethylformamide, THF. The condensing agent may be a condensing agent used in a usual peptide condensation method (for example, an acid chloride method, a mixed acid anhydride method, etc.), and among them, 1-hydroxybenzotriazole monohydrate and 1- (3 -(Dimethylamino) propyl) -3
A combination with -ethylcarbodiimide hydrochloride is preferred. Examples of the base include organic bases such as triethylamine and N-methylmorpholine, and triethylamine is preferable. The reaction temperature is usually -10 ° C to 6
The temperature is 0 ° C, preferably 0 ° C to room temperature. The reaction time is usually 10 minutes or longer, preferably 1 hour to 24 hours, more preferably 3 hours to 15 hours, and further preferably 3 hours to.
12 hours.

Step 1-4 The compound represented by the general formula (5) is subjected to a condensation reaction with the compound represented by the general formula (7) in a solvent using a condensing agent to give the compound represented by the general formula (8). The compound can be obtained. Examples of the solvent include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, and diglyme; hydrocarbon solvents such as benzene, toluene, hexane, and xylene; dichloromethane, chloroform, carbon tetrachloride, and 1 , 2-dichloroethane and other halogen-based solvents; methanol, ethanol,
Examples thereof include alcohol solvents such as isopropyl alcohol and tert-butanol; ester solvents such as ethyl acetate, methyl acetate and butyl acetate; polar solvents such as acetone, N, N-dimethylformamide, and dimethyl sulfoxide; Can be used together. The preferred solvent in this reaction is N, N-dimethylformamide. The condensing agent may be a condensing agent used in a usual peptide condensation method (for example, an acid chloride method, a mixed acid anhydride method), and among them, 1-hydroxybenzotriazole monohydrate and 1- (3- A combination with (dimethylamino) propyl) -3-ethylcarbodiimide hydrochloride is preferred. The reaction temperature is generally -30 ° C to 50 ° C, preferably -20 ° C to room temperature. The reaction time is usually 1 hour to 48 hours, preferably 12 hours to 24 hours.

Step 1-5 One of the target compounds is obtained by subjecting a compound represented by the general formula (8) to a condensation reaction with a compound represented by the general formula (4) in a solvent using a condensing agent. The compound represented by formula (1-2) can be obtained. Examples of the solvent include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, and diglyme; hydrocarbon solvents such as benzene, toluene, hexane, and xylene; dichloromethane, chloroform, carbon tetrachloride, and 1 , Halogenated solvents such as 2-dichloroethane;
Methanol, ethanol, isopropyl alcohol, t
Examples thereof include alcohol solvents such as ert-butanol; ester solvents such as ethyl acetate, methyl acetate and butyl acetate; polar solvents such as acetone, N, N-dimethylformamide, and dimethyl sulfoxide; and these may be used alone or in combination. You can The preferred solvent in this reaction is
It is N, N-dimethylformamide. The condensing agent may be a condensing agent used in a usual peptide condensation method (eg, acid chloride method, mixed acid anhydride method), and among them, 1-hydroxybenzotriazole monohydrate and 1-hydroxybenzotriazole monohydrate
A combination with (3- (dimethylamino) propyl) -3-ethylcarbodiimide hydrochloride is preferred. The reaction temperature is generally -30 ° C to 50 ° C, preferably -20 ° C to room temperature. The reaction time is generally 1 hour to 48 hours, preferably 1 hour to 24 hours.

Step 1-6 The compound represented by the general formula (6) is dissolved in a solvent to give the compound represented by the general formula (9):
A compound represented by the general formula (1-3), which is one of the target compounds, can be obtained by reacting with a compound represented by or a reagent equivalent thereto (for example, methylbenzimidate hydrochloride, etc.). it can. As the solvent, for example,
Diethyl ether, tetrahydrofuran, dioxane,
Ether-based solvents such as 1,2-dimethoxyethane and diglyme; hydrocarbon-based solvents such as benzene, toluene, hexane and xylene; halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride and 1,2-dichloroethane; methanol and ethanol , Isopropyl alcohol, ter
Alcohol solvents such as t-butanol; ester solvents such as ethyl acetate, methyl acetate, butyl acetate; acetone;
Examples thereof include polar solvents such as N, N-dimethylformamide and dimethyl sulfoxide, which can be used alone or in combination. The preferred solvent in this reaction is methanol. The reaction temperature is generally -30 ° C to 50 ° C, preferably 0 ° C to room temperature. Reaction time is usually 3 hours to 48
The time is preferably 12 hours to 24 hours.

Production Method 2 The compound represented by the general formula (1) is combined with the nitrogen atom to which R ⁶ and R ⁷ are bonded,

[Chemical 53] (In the formula, Z, R ^36, and R ³⁷ are the same as the above), and will be exemplified below.

[Chemical 54]

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ^{6 ′} , R ^{44 ′} and ring D are the same as defined above, R ^{6 ′}
Is a hydrogen atom, a C _1-6 alkyl group or an aralkyl group (the aralkyl group may be substituted with a halogen atom), and R ^{36 ′} and R ^{37 ′} are a hydrogen atom, a halogen atom, C _1-6. An alkyl group, a C _1-6 alkoxy group or a hydroxyl group, and R ^{42 ′} is a C _1-6 alkyl group).

Step 2-1 Among the compounds represented by the general formula (1-2) obtained in Step 1-3 or 1-5, ring D is

[Chemical 55] (Where R^{12 '}And R^{13 '}Are the same or different
Respectively hydrogen atom, halogen atom, C_1-6Archi
Lu group, C_1-6An alkoxy group or a hydroxyl group (R
^{12 '}And R^{13 '}Is R^{36 '}And R^{37 '}Synonymous with
Yes, R⁴⁴Is the same as above)
In a solvent, a phosgene equivalent (for example, carbodiimidazo
, Triphosgene, etc., preferably triphosgene)
Reaction is carried out, and one of the target compounds
The compound represented by general formula (1-4) can be obtained.
In addition to the above two types of reagents, diphosgene,
Ethyl chlorocarbonate or the like can be used. Used for reaction
Examples of the solvent include diethyl ether and tetrahydo.
Drofuran, dioxane, 1,2-dimethoxyethane,
Ether-based solvents such as diglyme; benzene, toluene,
Hydrocarbon solvents such as xane and xylene; dichlorometa
N, chloroform, carbon tetrachloride, 1,2-dichloroethane
Halogen-based solvents such as methanol; ethanol, iso
Alcohol such as propyl alcohol and tert-butanol
Solvent such as ethyl acetate, methyl acetate, butyl acetate, etc.
Ester-based solvent; acetone, N, N-dimethylformua
Examples include polar solvents such as amide, dimethyl sulfoxide, and water.
These can be used alone or in combination. This reaction
The preferred solvent in is N, N-dimethylformamid.
It is a mixed liquid of THF, THF and water. In addition, this reaction
Use is preferred. Examples of the base that can be used include water.
Sodium oxide, sodium hydrogen carbonate (baking soda), carbonate
Inorganic bases such as lithium; triethylamine, diazabisic
Loundecene, 1,8-diazabicyclo [5.4.0]
An organic base such as undeca-7-ene, preferably charcoal.
Sodium hydrogenate. The reaction temperature is usually -10 ° C to 6
The temperature is 0 ° C, preferably 0 ° C to room temperature. Reaction time is normal
1 hour or more, preferably 1 to 24 hours, more preferable
It is preferably 3 to 24 hours, preferably 6 to 12 hours
It's time.

Step 2-2 Among the compounds represented by the general formula (1-2) obtained in Step 1-3 or 1-5, ring D is

[Chemical 56] (Wherein R ^{12 ′} and R ^{13 ′} have the same meanings as described above)
By subjecting the compound represented by the formula (1) to the same reaction as in step 2-1, a compound represented by the general formula (1-5), which is one of the target compounds, can be obtained.

Step 2-3 Of the compounds represented by the general formula (1-2) obtained in Step 1-3 or 1-5, ring D is

[Chemical 57] (Wherein R ^{12 ′} , R ^{13 ′} and R ^{44 ′} are the same as the above), by reacting with a thiocarbonyl compound in a solvent, a compound represented by the general formula ( The compound represented by 1-6) can be obtained. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and diglyme; hydrocarbon solvents such as benzene, toluene, hexane and xylene; dichloromethane, chloroform and tetrachloride. Carbon 1,
Halogen-based solvent such as 2-dichloroethane; methanol,
Alcohol solvents such as ethanol, isopropyl alcohol, tert-butanol; ester solvents such as ethyl acetate, methyl acetate, butyl acetate; acetone, N, N
-Dimethylformamide, dimethylsulfoxide, polar solvents such as water and the like can be mentioned, and these can be used alone or in combination. The preferred solvent in this reaction is tetrahydrofuran. Examples of the thiocarbonyl compound include thiocarbonyldiimidazole, carbon disulfide, thiophosgene and the like, preferably thiocarbonyldiimidazole. In this reaction, it may be desired to use a base. Examples of the base used include inorganic bases such as sodium hydroxide, sodium hydrogen carbonate and potassium carbonate; organic bases such as triethylamine and 1,8-diazabicyclo [5.4.0] undec-7-ene. The reaction temperature is generally -10 ° C to 60 ° C, preferably 0 ° C to room temperature. The reaction time is usually 1 hour to 12 hours, preferably 2 hours to 6 hours.

Step 2-4 Among the compounds represented by the general formula (1-2) obtained in Step 1-3 or 1-5, ring D is

[Chemical 58] (Wherein R ^{12 ′} and R ^{13 ′} are the same as above), the compound of interest is reacted with orthoacetic acid ester or formic acid or its derivative in the presence of an acid in a solvent. A compound represented by the general formula (1-7) is obtained. Examples of the solvent include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme; hydrocarbon solvents such as benzene, toluene, hexane, xylene; dichloromethane, chloroform, carbon tetrachloride, 1 , Halogen solvents such as 2-dichloroethane; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol; ester solvents such as ethyl acetate, methyl acetate, butyl acetate;
Examples thereof include polar solvents such as acetone, N, N-dimethylformamide, dimethylsulfoxide, and formic acid, and these can be used alone or in combination. The preferred solvent in this reaction is N, N-dimethylformamide. Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid, sulfuric acid and nitric acid; organic acids such as trifluoroacetic acid, trichloroacetic acid, acetic acid, methanesulfonic acid and p-toluenesulfonic acid, and preferably methanesulfonic acid. is there. Methyl orthoacetate is preferred as the orthoacetate ester. Examples of formic acid and its derivatives include formic acid, ethyl orthoformate and the like, with formic acid being preferred. The reaction temperature is generally -10 ° C to 100 ° C, preferably 0 ° C to room temperature. The reaction time is usually 30 minutes to 12 hours, preferably 30 minutes to 6 hours, and more preferably 1 hour to 6 hours.

Step 2-5 Of the compounds represented by the general formula (1-2) obtained in Step 1-3 or 1-5, ring D is

[Chemical 59] (Wherein R ^{12 ′} and R ^{13 ′} are the same as above), the compound represented by the general formula (1-8), which is one of the target compounds, is obtained by reacting with formic acid under heating. The compound can be obtained. Reaction temperature is usually 80
C. to 300.degree. C., preferably 100.degree. C. to 200.degree. The reaction time is usually 4 hours to 24 hours, preferably 5 hours.
Hours to 12 hours.

Step 2-6 Among the compounds represented by the general formula (1-2) obtained in Step 1-3 or 1-5, ring D is

[Chemical 60] (Wherein R ^{12 ′} and R ^{13 ′} are the same as above)
The compound represented by is reacted with an acetyl halide compound (eg, acetyl chloride, acetyl bromide, etc.) in a solvent in the presence of an organic base (eg, pyridine, triethylamine, sodium hydrogen carbonate, etc.). Furthermore, the compound represented by the general formula (1-9), which is one of the target compounds, can be obtained by cyclizing the obtained compound without isolation, using a base, sodium iodide and the like. . Examples of the solvent in and include, for example, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme; hydrocarbon solvents such as benzene, toluene, hexane, xylene; dichloromethane, chloroform, carbon tetrachloride. A halogen-based solvent such as 1,2-dichloroethane;
Methanol, ethanol, isopropyl alcohol, t
Examples thereof include alcohol solvents such as ert-butanol; ester solvents such as ethyl acetate, methyl acetate and butyl acetate; polar solvents such as acetone, N, N-dimethylformamide, and dimethyl sulfoxide; and these may be used alone or in combination. You can The preferred solvent in this reaction is
Tetrahydrofuran, ethyl acetate or N, N-dimethylformamide, or a mixed solvent thereof. Examples of the base used in the reaction include alkali metal hydrides such as sodium hydride and potassium hydride; sodium ethoxide, sodium methoxide, potassium t
alk-alkoxides such as ert-butoxide; n
-Alkyl lithium such as butyl lithium and sec-butyl lithium; alkali metal amides such as lithium diisopropylamide, sodium amide and lithium bistrimethylsilyl azide; alkali metal carbonates such as sodium carbonate and potassium carbonate; sodium hydrogen carbonate, potassium hydrogen carbonate and the like Alkali metal hydrogen carbonate of lithium; lithium hydroxide,
Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; Carboxylic acid alkali metal salts such as sodium acetate and potassium acetate; Phosphorus alkali metal salts such as sodium phosphate and potassium phosphate; Triethylamine, pyridine, N-methyl Examples thereof include organic bases such as morpholine and 1,8-diazabicyclo [5.4.0] undec-7-ene, and potassium carbonate is preferable. The reaction temperature is generally -30 ° C to 100 ° C, preferably 0 ° C to 80 ° C, preferably 0 ° C to room temperature. Reaction time is usually 1 to 2
It is 4 hours, preferably 1 hour to 15 hours, preferably 2 hours to 12 hours.

Step 2-7 Among the compounds represented by the general formula (1-2) obtained in Step 1-3 or 1-5, ring D is

[Chemical formula 61] (Wherein R ^{12 ′} and R ^{13 ′} have the same meanings as described above) are cyclized in a solvent in the presence of a condensing agent to give a compound represented by the general formula (1) −
The compound represented by 10) can be obtained. Examples of the solvent include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, and diglyme; benzene, toluene, hexane, and the like.
Hydrocarbon solvent such as xylene; halogen solvent such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane; alcohol solvent such as methanol, ethanol, isopropyl alcohol, tert-butanol; ethyl acetate, methyl acetate, acetic acid Ester solvents such as butyl; polar solvents such as acetone, N, N-dimethylformamide, dimethylsulfoxide and the like can be mentioned, and these can be used alone or in combination. The preferred solvent in this reaction is N, N-dimethylformamide. The condensing agent may be a condensing agent used in a usual peptide condensation method (for example, an acid chloride method, a mixed acid anhydride method, etc.), and among them, 1-hydroxybenzotriazole monohydrate and 1- (3 -(Dimethylamino) propyl) -3
A combination with -ethylcarbodiimide hydrochloride is preferred. The reaction temperature is generally -30 ° C to 60 ° C, preferably 0.
C to room temperature. The reaction time is usually 5 hours to 24 hours,
It is preferably 10 hours to 20 hours.

Production Method 3 The compound represented by the general formula (1) is combined with a nitrogen atom in which R ⁶ and R ⁷ are adjacent to each other,

[Chemical formula 62] (In the formula, W, R ^{38 ′} , R ³⁹ and R ⁴⁰ have the same meanings as described above, and R ^{38 ′} is an aryl group).

[Chemical formula 63]

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ^{6 ′} , R ^{38 ′} , R ³⁹ and R ⁴⁰ have the same meanings as described above, and boc is a tert-butoxycarbonyl group).

Step 3-1 The compound represented by the general formula (6) obtained in step 1-2 and the compound represented by the general formula (10) are subjected to the same condensation reaction as in step 1-3. The compound represented by the general formula (11) can be obtained.

Step 3-2 The tert-butoxycarbonyl group of the compound represented by the general formula (11) is converted to an acid (eg, trifluoroacetic acid, hydrochloric acid,
After deprotecting with hydrobromic acid, p-toluenesulfonic acid, etc.), the obtained amino compound is cyclized with a phosgene equivalent (eg, carbonyldiimidazole, triphosgene, etc.) in the presence of a base, A compound represented by the general formula (1-11), which is one of the target compounds, can be obtained. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and diphenyl ether; hydrocarbon solvents such as benzene, toluene, hexane and xylene; dichloromethane, chloroform, Halogen-based solvents such as carbon tetrachloride, chlorobenzene and 1,2-dichloroethane; alcohol-based solvents such as methanol, ethanol, isopropyl alcohol and tert-butanol; polar solvents such as N, N-dimethylformamide, dimethylsulfoxide and water. These may be used alone or in combination, or may be solventless. The preferred solvent used in this reaction is tetrahydrofuran. As the base used in the reaction,
For example, alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal alkoxides such as sodium ethoxide, sodium methoxide and potassium tert-butoxide; alkyl lithium such as n-butyl lithium and sec-butyl lithium; lithium diisopropyl Alkali metal amides such as amide, sodium amide and lithium bistrimethylsilylamide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; lithium hydroxide, sodium hydroxide, Alkali metal hydroxides such as potassium hydroxide; Carboxylic acid alkali metal salts such as sodium acetate and potassium acetate; Phosphate alkali metal salts such as sodium phosphate and potassium phosphate; Triethylamine, pyri Emissions, N- methylmorpholine, 1,8
Examples include organic bases such as diazabicyclo [5.4.0] undec-7-ene, and triethylamine is preferable. The reaction temperature is generally 0 ° C to 100 ° C, preferably room temperature to 60 ° C. The reaction time is usually 1 hour to 48 hours, preferably 1 hour to 25 hours, more preferably 2 hours to 24 hours.

Step 3-3 In the same manner as in Step 3-2, the tert-butoxycarbonyl group of the compound represented by the general formula (11) is converted into an acid (for example,
After deprotection with trifluoroacetic acid, hydrochloric acid, etc.), cyclization with a thiocarbonylating reagent (eg, thiocarbonyldiimidazole, carbon disulfide, thiophosgene, etc.) in the presence of a base gives one of the target compounds. A general formula (1-
The compound represented by 12) can be obtained.

Step 3-4 A compound represented by the general formula (14) is obtained by reacting a compound represented by the general formula (12) with a compound represented by the general formula (13) in acetonitrile. be able to. The reaction temperature is generally 50 ° C to 200 ° C, preferably 80 ° C to 100 ° C. Reaction time is usually 1 hour to 10
The time is preferably 2 hours to 5 hours.

Step 3-5 In the same manner as in Step 1-3, the compound represented by the general formula (6) is reacted with the compound represented by the general formula (14) to give the compound represented by the general formula (15). The compound can be obtained.

Step 3-6 The compound represented by the general formula (15) is cyclized with a phosgene equivalent (eg, triphosgene, carbonyldiimidazole, diphosgene, etc.) in a solvent in the presence of a base to give the desired compound. A compound represented by one general formula (1-13) can be obtained. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and diphenyl ether; hydrocarbon solvents such as benzene, toluene, hexane and xylene; dichloromethane, chloroform, Chlorobenzene,
Halogen-based solvents such as carbon tetrachloride and 1,2-dichloroethane; alcohol-based solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol; N,
Examples thereof include N-dimethylformamide, dimethyl sulfoxide, polar solvents such as water, dimethylaniline and the like, and these can be used alone or in combination, or can be used without solvent. The preferred solvent used in this reaction is tetrahydrofuran. As the base used in the reaction,
For example, alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal alkoxides such as sodium ethoxide, sodium methoxide and potassium tert-butoxide; alkyl lithium such as n-butyl lithium and sec-butyl lithium; lithium diisopropyl Alkali metal azides such as amides, sodium amides and lithium bistrimethylsilyl azide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; lithium hydroxide, sodium hydroxide, Alkali metal hydroxides such as potassium hydroxide; Carboxylic acid alkali metal salts such as sodium acetate and potassium acetate; Phosphate alkali metal salts such as sodium phosphate and potassium phosphate; Triethylamine, pyri Emissions, N- methylmorpholine, 1,8
Examples include organic bases such as diazabicyclo [5.4.0] undec-7-ene, and triethylamine is preferable. The reaction temperature is generally 0 ° C to 100 ° C, preferably 0 ° C.
C to room temperature. The reaction time is usually 1 hour to 24 hours,
It is preferably 4 hours to 10 hours.

Step 3-7 By cyclizing the compound represented by the general formula (15) with a formalin equivalent (eg, paraformaldehyde, dimethoxymethane, dibromomethane, etc.) in a solvent, one of the target compounds is obtained. A compound represented by a certain general formula (1-14) can be obtained. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and diphenyl ether; benzene, toluene,
Hydrocarbon solvents such as hexane and xylene; dichloromethane, chloroform, carbon tetrachloride, chlorobenzene, 1,
Halogen-based solvent such as 2-dichloroethane; methanol,
Examples thereof include alcohol solvents such as ethanol, isopropyl alcohol and tert-butanol; polar solvents such as N, N-dimethylformamide, dimethylsulfoxide and water; and dimethylaniline. These can be used alone or in combination, or none. A solvent is also possible. Preferred solvents used in this reaction are methanol and ethanol. This reaction is preferably carried out in the presence of acid or base. The reaction temperature is generally 0 ° C to 100 ° C, preferably 0 ° C to room temperature. The reaction time is usually 1 hour to 10 days,
It is preferably 1 to 10 days, more preferably 1 to 3 days. The compound represented by the general formula (1-14) (provided that R ^{38 ′} is a hydrogen atom) can be produced by the following method as well as the method in the above step 3-7. :formula

[Chemical 64] (Wherein each symbol has the same meaning as described above), the compound represented by the formula is reduced. The reduction can be carried out by a conventional method. For example, a desired compound can be produced by reacting a compound represented by the general formula (1-14 ′) with a reducing agent such as sodium cyanoborohydride. it can.

Production Method 4 The compound represented by the general formula (1) is combined with a nitrogen atom in which R ⁶ and R ⁷ are adjacent to each other,

[Chemical 65] (In the formula, V ₁ , V ₂ and V ₃ are the same as above), and the case is illustrated below.

[Chemical formula 66]

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ^{5 ′} and R ⁴⁶ are the same as above, and boc is ter
It is a t-butoxycarbonyl group).

Step 4-1 Similarly to Step 1-3, the compound represented by the general formula (6) is reacted with the compound represented by the general formula (16) to give the compound represented by the general formula (17). The compound can be obtained.

Step 4-2 This is a deprotection reaction of an amino-protecting group which is usually carried out. The compounds represented can be obtained. Examples of the solvent include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, and diglyme; hydrocarbon solvents such as benzene, toluene, hexane, and xylene; dichloromethane, chloroform, carbon tetrachloride, and 1 ，
Halogen-based solvent such as 2-dichloroethane; methanol,
Alcohol solvents such as ethanol, isopropyl alcohol, tert-butanol; ester solvents such as ethyl acetate, methyl acetate, butyl acetate; acetone, N, N
-Polar solvents such as dimethylformamide and dimethylsulfoxide are listed, and these can be used alone or in combination. A preferred solvent in this reaction is dioxane,
Dichloroethane and trifluoroacetic acid. Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and nitric acid; trifluoroacetic acid, trichloroacetic acid, acetic acid,
Examples thereof include organic acids such as methanesulfonic acid and p-toluenesulfonic acid, and trifluoroacetic acid is preferable. The reaction temperature is generally -10 ° C to 60 ° C, preferably 0 ° C to 60 ° C.
C, more preferably 0 C to room temperature. The reaction time is usually 1 hour or longer, preferably 1 to 20 hours, more preferably 1 to 12 hours, and further preferably 4 to 6 hours.
It's time.

Step 4-3 The compound represented by the general formula (18) is cyclized with a phosgene equivalent (eg, carbonyldiimidazole, triphosgene, diphosgene, ethyl chlorocarbonate) in a solvent to give the desired compound. A compound represented by one general formula (1-15) can be obtained. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and diphenyl ether; hydrocarbon solvents such as benzene, toluene, hexane and xylene; dichloromethane, chloroform, Carbon tetrachloride, 1,
Halogen-based solvents such as 2-dichloroethane and chlorobenzene; alcohol-based solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol; N,
Examples thereof include polar solvents such as N-dimethylformamide, dimethylsulfoxide and water, and these can be used alone or in combination, or can be used without solvent. The preferred solvent used in this reaction is tetrahydrofuran. In this reaction, when a base is used, the reaction may proceed smoothly. The reaction temperature is usually -10 ° C to 10
The temperature is 0 ° C, preferably 0 ° C to room temperature. The reaction time is usually 0.5 hours to 24 hours, preferably 1 hour to 3 hours.

Step 4-4 In the same manner as in Step 1-3, the compound represented by the general formula (6) is reacted with the compound represented by the general formula (19) to obtain the compound represented by the general formula (20). The compound can be obtained.

Step 4-5 In the same manner as in Step 4-3, the compound represented by the general formula (20) is converted into a phosgene equivalent (eg, carbonyldiimidazole, triphosgene, diphosgene, ethyl chlorocarbonate, etc.).
By cyclizing with, a compound represented by the general formula (1-16), which is one of the target compounds, can be obtained.

Step 4-6 In the same manner as in Step 3-3, the compound represented by the general formula (20) is cyclized with a thiocarbonylating reagent (eg, thiocarbonyldiimidazole, carbon disulfide, thiophosgene, etc.). Thus, the general formula (1-
The compound represented by 17) can be obtained.

Step 4-7 In the same manner as in Step 3-7, the compound represented by the general formula (20) is cyclized with a formalin equivalent (eg, paraformaldehyde, dimethoxymethane, dibromomethane, etc.), The general formula (1-1) which is one of the target compounds
The compound represented by 8) can be obtained.

Step 4-8 In the same manner as in Step 1-3, the compound represented by the general formula (6) is reacted with the compound represented by the general formula (21) to give the compound represented by the general formula (22). The compound can be obtained.

Step 4-9 By reacting the compound represented by the general formula (22) with 1,2-dibromoethane or 1,2-dichloroethane in a solvent in the presence of a base, one of the target compounds is obtained. A compound represented by a certain general formula (1-19) can be obtained. Either 1,2-dibromoethane or 1,2-dichloroethane is used in the reaction. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and diphenyl ether; hydrocarbon solvents such as benzene, toluene, hexane and xylene; halogens such as chlorobenzene. Solvents; methanol, ethanol, isopropyl alcohol, tert-
Examples thereof include alcohol solvents such as butanol; polar solvents such as N, N-dimethylformamide and dimethyl sulfoxide, and these can be used alone or in combination, or can be used without solvent. The preferred solvent used in this reaction is N, N-dimethylformamide. Examples of the base used in the reaction include sodium hydride,
Alkali metal hydrides such as potassium hydride; sodium ethoxide, sodium methoxide, potassium tert.
-Alkali metal alkoxides such as butoxide; Alkyl lithium such as n-butyl lithium and sec-butyl lithium; Alkali metal amides such as lithium diisopropylamide, sodium amide and lithium bistrimethylsilylamide; Alkali metal carbonates such as sodium carbonate and potassium carbonate Alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; carboxylic acid alkali metal salts such as sodium acetate and potassium acetate; phosphoric acid Alkali metal phosphates such as sodium and potassium phosphate; triethylamine, pyridine, N
-Methylmorpholine, 1,8-diazabicyclo [5.
4.0] organic bases such as undeca-7-ene,
Preferred is potassium carbonate. The reaction temperature is usually 0 ° C
The temperature is 100 ° C, preferably room temperature to 70 ° C. The reaction time is usually 1 hour to 48 hours, preferably 2 hours to 24 hours.
It's time.

Production Method 5 In the compound represented by the general formula (1), R ⁷ is —C (═O).
-A'- ring D (wherein, A 'is ^{-N (R 8) -, -} C (R
⁹ ) (R ¹⁰ )-or —CO— and ring D has the same meaning as above), the production method is illustrated below.

[Chemical formula 67]

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ^{6 ′} , R ⁹ , R ¹⁰ and ring D are the same as above)

Step 5-1 One of the target compounds is obtained by reacting the compound represented by the general formula (6) obtained in step 1-2 with the compound represented by the general formula (23) in a solvent. Is a general formula (1-2
A compound represented by 0) can be obtained. Examples of the solvent used in the reaction include diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane,
Ether-based solvents such as diglyme and diphenyl ether; hydrocarbon-based solvents such as benzene, toluene, hexane and xylene; halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene and 1,2-dichloroethane; methanol, ethanol, isopropyl alcohol , Tert-butanol and other alcohol solvents; N,
Examples thereof include polar solvents such as N-dimethylformamide and dimethyl sulfoxide, and dimethylaniline. These can be used alone or in combination, or can be used without solvent. The preferred solvent used in this reaction is dioxane. The reaction temperature is generally 0 ° C to 100 ° C, preferably room temperature to 80 ° C. Reaction time is usually 1 hour to 1
It is 2 hours, preferably 1 hour to 6 hours, more preferably 2 hours to 6 hours.

Step 5-2 In the same manner as in Step 5-1, the compound represented by the general formula (6) is reacted with the compound represented by the general formula (24) to give one of the target compounds. A compound represented by the general formula (1-21) can be obtained.

Step 5-3 A compound represented by the general formula (6) is reacted with a compound represented by the general formula (25) in a solvent in the presence of a base to give one of the target compounds. A compound represented by the formula (1-22) can be obtained. Examples of the solvent used in the reaction include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and diphenyl ether; hydrocarbon solvents such as benzene, toluene, hexane and xylene; dichloromethane, chloroform, Halogen-based solvents such as carbon tetrachloride, chlorobenzene and 1,2-dichloroethane; alcohol-based solvents such as methanol, ethanol, isopropyl alcohol and tert-butanol; N,
Examples thereof include polar solvents such as N-dimethylformamide and dimethylsulfoxide, which can be used alone or in combination, or can be used without solvent. The preferred solvent used in this reaction is tetrahydrofuran. Examples of the base used in the reaction include alkali metal hydrides such as sodium hydride and potassium hydride; sodium ethoxide, sodium methoxide, potassium t
alk-alkoxides such as ert-butoxide; n
-Butyl lithium, sec-butyl lithium, etc. alkyl lithium; sodium carbonate, potassium carbonate, etc. alkali metal carbonates; sodium hydrogen carbonate, potassium hydrogen carbonate, etc. alkali metal hydrogen carbonates; lithium hydroxide, sodium hydroxide, hydroxide Alkali metal hydroxides such as potassium; Carboxylic acid alkali metal salts such as sodium acetate and potassium acetate; Phosphate alkali metal salts such as sodium phosphate and potassium phosphate; Triethylamine, pyridine, N
-Organic bases such as methylmorpholine are mentioned, and triethylamine is preferable. The reaction temperature is usually 0 ° C to 10 ° C.
The temperature is 0 ° C, preferably room temperature to 60 ° C. The reaction time is usually 1 hour to 12 hours, preferably 1 hour to 6 hours, more preferably 2 hours to 6 hours.

Step 5-4 In the same manner as in Step 1-3, the compound represented by the general formula (6) is reacted with the compound represented by the general formula (26) to give one of the target compounds. The compound represented by the general formula (1-23) can be obtained. When a salt of the compound (1) of the present invention is desired, the free compound (1) of the present invention obtained by the above production methods 1 to 5 can be converted into a salt according to a conventional method.

[0092]

The present invention will be described in detail below with reference to examples, but the present invention is not limited thereto. still,
In the following formula, "boc" means tert-butoxycarbonyl.

Example 1 Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide a) 5-chloro-1H-indole-2-carboxylic acid
Hydrazide 5-chloro-1H-indole-2-carboxylic acid (1.
96 g) and 1-hydroxybenzotriazole monohydrate (HOBt.H ₂ O) (1.58 g) were dissolved in N, N-dimethylformamide (DMF) (10 ml), and 1- (3- (dimethyl) was added thereto. Amino) propyl) -3-ethylcarbodiimide hydrochloride (EDC) (2.58g) was added. The solution was stirred at room temperature for 3 hours. The solution was cooled in an ice bath and hydrazine hydrate (2.4 ml) was added. The solution was stirred at room temperature for 11 hours. Water (20 ml) was slowly added to the reaction solution. The precipitated solid was collected by filtration and dried under reduced pressure to give the title compound (2.24 g) (DMF
15% as residual solvent) was obtained. A purer sample could be obtained by boiling this sample in tetrahydrofuran (THF), allowing it to cool, and collecting it by filtration. ¹ H-NMR (δ value, 300 MHz, DMSO-
d _6). 4.52 (2H, brs), 7.05 (1H, d, J =
1.5Hz), 7.16 (1H, dd, J = 8.7H
z, 2.1 Hz), 7.42 (1H, d, J = 8.7H
z), 7.66 (1H, d, J = 1.9 Hz), 9.8
6 (1H, brs), 11.84 (1H, s).

B) Benzoic acid 2- (5-chloro-1H-)
Indole-2-carbonyl) hydrazide 5-chloro-1H-indole-2-carboxylic acid hydrazide obtained in Example 1 a) (98 mg) was added to THF.
It was suspended in (2 ml) and triethylamine (73 μl) was added. The mixture was cooled in an ice bath and benzoyl chloride (61 μl) was added slowly to it. The reaction solution was stirred at room temperature for 10 minutes. Ethyl acetate (5 ml), TH
F (3 ml) and ice water (10 ml) were added and stirred. The separated organic layer was added with an aqueous solution of sodium hydroxide (0.1
N), washed successively with water, and dried over anhydrous sodium sulfate. When this solution was filtered and concentrated, white crystals were precipitated. This was collected by filtration and dried under reduced pressure to give the title compound (29 mg)
Was obtained (see Table 1).

Example 1-2 2-Amino-benzoic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide 5-chloro-1H-indole obtained in Example 1 a)
Le-2-carboxylic acid hydrazide (6.00 g), ant
Ranilic acid (3.42 g) and HOBt · H _TwoO (3.
882 g) in a mixed solution of DMF (100 ml)
EDC (4.79 g) was added. This mixture at room temperature
Stir the day. THF (200 ml), half-saturated food in the reaction solution
Brine (200 ml) was added. Hydroxylate the separated organic layer
Aqueous sodium solution (0.1N), hydrochloric acid water (0.5N),
It was sequentially washed with pure water. This solution over anhydrous sodium sulfate
It was dried and filtered. Concentrate this solution to a small amount and leave
And a white powder was deposited. This is collected by filtration and dried under reduced pressure to give the title.
A compound (4.35 g, yield 55%) was obtained (see Table 1).
See).

Example 1-3 2-Hydroxy-benzoic acid 2- (5-chloro-1H-)
Indole-2-carbonyl) hydrazide The title compound was obtained as crystals by the same method as in Example 1-2, but using salicylic acid instead of anthranilic acid (see Table 1).

Example 1-4 3-[{2- (2- (5-chloro-1H-indole-
2-Carbonyl) hydrazinocarbonyl) phenyl} carbamoyloxy] -2,2-dimethylpropionic acid a) 3-hydroxy-2,2-dimethylpropionic acid
Benzyl ester hydroxypivalic acid (5.03 g) was added to DMF (50 m
l), benzyl bromide (5.50 ml) and potassium carbonate (11.38 g) were sequentially added, and the mixture was stirred at room temperature for 12 hours.
Stir for hours. Water (100 ml) was added to the reaction mixture, followed by extraction with ether (2 × 100 ml), and the organic layer was water (2 × 50 ml) and saturated sodium chloride aqueous solution (50 m).
It was washed successively with 1), dried and concentrated under reduced pressure. The obtained oil was purified by column chromatography to give the title compound (6.54 g) as a colorless oil. ¹ H-NMR (δ value, 300 MHz, CDCl ₃ ) 1.22 (6 H, s), 2.37 (1 H, t, J = 6.
8Hz), 3.58 (2H, d, J = 6.8Hz),
5.15 (2H, s), 7.30-7.40 (5H,
m).

B) 2- (2-Benzyloxycarbonyl-2-methylpropoxycarbonylamino) benzoic acid phthalic acid tert-butyl ester (5.38 g) was dissolved in toluene (50 ml). Triethylamine (3.7 ml) and diphenylphosphoric acid azide (5.7 ml) were sequentially added to this solution, and the temperature was raised to 130 ° C. and the mixture was stirred for 1 hour. After allowing the reaction mixture to cool to room temperature, Example 1
-4- 3-hydroxy-2,2-dimethylpropionic acid benzyl ester (4.95 g) obtained in a) was added, and the mixture was stirred at room temperature for 17 hours. The reaction mixture was diluted with ethyl acetate (50 ml), washed successively with water (50 ml) and saturated aqueous sodium chloride solution (5 ml), dried and concentrated under reduced pressure. The oily substance obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate = 1: 1). The purified oil (3.28 g) was dissolved in dichloromethane (30 ml). This solution was cooled to 0 ° C., trifluoroacetic acid (30 ml) was added, the temperature was raised to room temperature, and the mixture was stirred for 3 hours. The reaction mixture was concentrated under reduced pressure, water (50 ml) was added, and ethyl acetate (150 ml) was added.
It was extracted with. The organic layer was washed successively with water (50 ml × 3) and saturated aqueous sodium chloride solution (50 ml), dried and concentrated under reduced pressure. The obtained oily matter was purified by column chromatography to give the title compound (2.54 g, yield 89
%) As a colorless oil. ¹ H-NMR (δ value, 300 MHz, DMSO-d ₆ ) 1.22 (6 H, s), 4.20 (2 H, s), 5.1
3 (2H, s), 7.12 (1H, m), 7.25-
7.34 (5H, m), 7.60 (1H, m), 7.9
9 (1H, dd, J = 1.6, 7.9 Hz), 8.23
(1H, d, J = 7.9 Hz), 10.72 (1H,
s), 13.63 (1H, brs).

C) 3-[{2- (2- (5-chloro-
1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl} carbamoyloxy] -2,2-dimethylpropionic acid benzyl ester 5-chloro-1H-indole-2-carboxylic acid hydrazide obtained in a) of Example 1 (Including 14% DMF)
(1.59 g), obtained in Example 1-4 b) 2-
(2-Benzyloxycarbonyl-2-methylpropoxycarbonylamino) benzoic acid (2.54g) and HO
Bt.H ₂ O (1.23 g) was dissolved in DMF (25 ml). EDC (1.59 g) was added to this solution, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate (150
ml), washed with water (50 ml) and saturated aqueous sodium chloride solution (50 ml). The solution was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained solid was slurry-washed with ether to give the title compound (2.58 g,
Yield 78%) was obtained as colorless amorphous. ¹ H-NMR (σ value, 300 MHz, DMSO-d ₆ ) 1.20 (6 H, s), 4.18 (2 H, s), 5.1
1 (2H, s), 7.14-7.29 (8H, m),
7.48 (1H, d, J = 8.8Hz), 7.60 (1
H, d, J = 7.3 Hz), 7.77 (1H, d, J =
1.8 Hz), 7.91 (1H, d, J = 7.3H)
z), 8.24 (1H, d, J = 8.4 Hz), 10.
62 (1H, s), 10.72 (1H, s), 10.8
2 (1H, s), 11.97 (1H, s).

D) 3-[{2- (2- (5-chloro-
1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl} carbamoyloxy] -2,2-dimethylpropionic acid 3-[{2- (2- (5
-Chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl} carbamoyloxy]-
2,2-Dimethylpropionic acid benzyl ester (1.64 g) was dissolved in THF (50 ml). To this solution was added 10% palladium-carbon (224 mg),
After making it into a hydrogen atmosphere, it stirred at room temperature for 6 hours and 30 minutes. The reaction mixture was filtered through a glass filter covered with Celite, the residue was washed with THF (25 ml), and the filtrate and the washing solution were combined and concentrated under reduced pressure. The obtained solid was crystallized from ethanol to give the title compound (831 mg, yield 60
%) As colorless needle crystals (see Table 1).

Example 1-5 Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) -1-methylhydrazide a) Benzoic acid 1-Methylhydrazide Benzoic acid (500 mg) in DMF solution (10 ml),
1-hydroxybenzotriazole (752 mg), E
DC (942 mg) was added. After stirring at room temperature for 3 hours, methyl hydrazine (2.18 m
l) was added. After stirring at room temperature for 16 hours, water was added. This mixture was extracted with ethyl acetate, and the organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, and dried over sodium sulfate. This solution was filtered and concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (n
-Hexane: ethyl acetate = 1: 2) to give the title compound (213 mg, yield 35%). ¹ H-NMR (δ value, 300 MHz, DMSO-
d _6). 3.16 (3H, s), 4.77 (1H, brs),
5.10 (1H, brs), 7.32-7.52 (5
H, m).

B) Benzoic acid 2- (5-chloro-1H)
-Indole-2-carbonyl) -1-methylhydrazide 5-chloro-1H-indole-2-carboxylic acid (10
0 mg) and the benzoic acid 1 obtained in Example 1-5 a) 1.
-Methylhydrazide (130 mg) in DMF (10
ml), 1-hydroxybenzotriazole (122
mg) and EDC (153 mg) were added. After stirring at room temperature for 16 hours, water was added to the reaction solution. The precipitated solid was collected by filtration and washed with water and diethyl ether. The filtered material was dried under reduced pressure to obtain the title compound (144 mg, yield 66%) (see Table 1).

Examples 1-6 Benzoic acid 2- (1-Acetyl-5-chloro-1H-indole-2-carbonyl) hydrazide a) 1-Acetyl-5-chloro-1H-indole-2
-Carboxylic acid 5-chloro-1H-indole-2-carboxylic acid (5.
50 g) was dissolved in anhydrous DMF (50 ml) and cooled with ice. Sodium hydride (oil, 60%) was added to this solution.
(2.35 g) was added, and the mixture was stirred at room temperature for 20 minutes. This solution was cooled in an ice bath again, and then acetyl chloride (2.3 ml)
Was dripped. The solution was stirred at room temperature for 1 hour and then cooled in an ice bath. After acetic acid (4 ml) was added to this solution, ethyl acetate and ice water (200 ml) were added. The separated organic layer was washed with water and then dried over anhydrous sodium sulfate. The extract was filtered, concentrated, and the concentrated solution was allowed to stand to obtain pale yellow crystals. This was collected by filtration and dried under reduced pressure to give the title compound (3.12 g, yield 49%). ¹ H-NMR (δ value, 300 MHz, DMSO-
d _6). 2.77 (3H, s), 7.37 (3H, s), 7.4
9 (1H, m), 7.82 (1H, m), 7.97 (1
H, d)

B) Benzoic acid 2- (1-acetyl-5)
-Chloro-1H-indole-2-carbonyl) hydrazide In the same manner as in b) of Example 1-5, 1-acetyl-5-
The title compound (17% yield) was obtained by reacting chloro-1H-indole-2-carboxylic acid with benzoic acid hydrazide (see Table 1).

Example 1-7 5-Chloro-1H-indole-2-carboxylic acid 2-
(Imino-phenyl-methyl) hydrazide a) thiobenzimidic acid methyl ester hydroiodide thiobenzamide (10.0 g) in acetone (60
ml) was added methyl iodide (10.3 g) at room temperature. The solution was stirred at room temperature for 13 hours. The precipitated crystals were collected by filtration, washed with diethyl ether, and dried under reduced pressure to give the title compound (18.5 g, yield 91%).

B) 5-chloro-1H-indole-2
-Carboxylic acid 2- (imino-phenyl-methyl) hydrazide A suspension of 5-chloro-1H-indole-2-carboxylic acid hydrazide (70.0 g) obtained in Example 1 a) in methanol (MeOH) ( 700 ml), Example 1-
The thiobenzimidic acid methyl ester hydroiodide (84.2 g) obtained in 7 a) was added at room temperature. The suspension was stirred at room temperature for 19 hours. Aqueous sodium hydrogen carbonate was added to this reaction solution to make it alkaline, and the precipitated solid was collected by filtration, washed with water, and washed with diethyl ether. The filtered material was boiled in THF-MeOH, allowed to cool, and diisopropyl ether was added. The precipitated solid was collected by filtration and dried to give the title compound (76.8 g, yield 85%) (see Table 1).

Example 1-8 5-aminothiazole-4-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide a) 5-aminothiazole-4-carboxylic acid hydrazine Chem. Pharm. Bull, 19 (1) 119-
123 (5-amino-thiazole-4-carboxylic acid ethyl ester (4
60 mg) was dissolved in ethanol (7 ml). Hydrazine monohydrate (1.3 ml) was added to this solution, and the mixture was refluxed at 100 ° C. for 22 hours. The reaction mixture was cooled to room temperature and the resulting solid was collected by filtration and washed with ethanol. The solid was dried under reduced pressure to give the title compound (280 mg)
Got ¹ H-NMR (σ value, 300 MHz, DMSO-d6) 4.26 (2H, s), 7.07 (2H, s), 8.0
0 (1H, s), 8.83 (1H, s).

B) 5-Aminothiazole-4-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide 5-Chloro-1H-indole-2-similar to Example 1-2. The carboxylic acid and the 5-aminothiazole-4-carboxylic acid hydrazine obtained in a) of Example 1-7 were reacted to obtain the title compound (yield 79%) (see Table 1).

Examples 1-9 to 1-143 In the same manner as Examples 1 to 1-8, Examples 1-9 to 1-1.
43 compounds are obtained. The obtained compounds are shown in Tables 1-18.

[0110]

[Table 1]

[0111]

[Table 2]

[0112]

[Table 3]

[0113]

[Table 4]

[0114]

[Table 5]

[0115]

[Table 6]

[0116]

[Table 7]

[0117]

[Table 8]

[0118]

[Table 9]

[0119]

[Table 10]

[0120]

[Table 11]

[0121]

[Table 12]

[0122]

[Table 13]

[0123]

[Table 14]

[0124]

[Table 15]

[0125]

[Table 16]

[0126]

[Table 17]

[0127]

[Table 18]

Example 2 N- (1,2,3,4-tetrahydro-2,4-dioxoquinazolin-3-yl) -5-chloro-1H-indole-2-carboxamide Obtained in Example 1-2. 2-aminobenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydrazide (329 mg) and sodium hydrogen carbonate (168
mg) was suspended in a mixed solvent of THF (10 ml) and water (3 ml) and cooled in an ice bath. Triphosgene (168m
g) was added portionwise over 20 minutes. The reaction solution was stirred at room temperature for 1 hour. The separated organic layer was washed with half-saturated saline three times and dried over anhydrous sodium sulfate. The solution was filtered and concentrated to give an oil. By adding chloroform to this, the title compound (317
mg, yield 89%) was obtained as crystals (see Table 19).

Example 2-2 N- (1,2,3,4-tetrahydro-2,4-dioxobenzo [e] [1,3] oxazin-3-yl) -5
-Chloro-1H-indole-2-carboxamide 2 obtained in Example 1-3 analogously to Example 1-2
The title compound was obtained from 2- (5-chloro-1H-indole-2-carbonyl) hydrazide of -hydroxybenzoic acid (see Table 19).

Example 2-3 N- (1,2,3,4-tetrahydro-4-oxo-2
-Thioxoquinazolin-3-yl) -5-chloro-1H
-Indole-2-carboxamide 2-amino-benzoic acid 2-obtained in Example 1-2
(5-chloro-1H-indole-2-carbonyl)-
Hydrazide (1.31 g) was dissolved in THF (26 ml), thiocarbonyldiimidazole (867 mg) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solvent was evaporated under reduced pressure and the obtained residue was dissolved in ethyl acetate. This solution was washed successively with water, hydrochloric acid (0.5N), saturated aqueous sodium hydrogen carbonate and water. The solution was dried over anhydrous sodium sulfate and filtered. The residue obtained by evaporating the filtrate under reduced pressure was crystallized from ethyl acetate and diethyl ether to give the title compound (91
0 mg, yield 61.3%) was obtained as pale yellow crystals (see Table 19).

Example 2-4 5-Chloro-1H-indole-2-carboxylic acid (2
-Methyl-4-oxo-4H-quinazolin-3-yl)
-Amid 2-amino-benzoic acid 2-obtained in Example 1-2
(5-chloro-1H-indole-2-carbonyl)-
Hydrazide (90 mg) was dissolved in DMF (1 ml). Methyl orthoacetate (3 ml) and methanesulfonic acid (0.05 ml) were sequentially added to this solution, and the mixture was stirred at room temperature for 30 minutes. Water (2 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate-THF (1: 1) (50 ml). The organic layer was washed successively with water (2 × 20 ml) and saturated aqueous sodium chloride solution (20 ml), dried and concentrated under reduced pressure. The obtained solid was slurry-washed with ether to give the title compound (77 mg, yield 80%) as a colorless solid (Table 1)
9).

Example 2-5 5-Chloro-1H-indole-2-carboxylic acid (4
-Oxo-4H-quinazolin-3-yl) -amide 2-amino-benzoic acid 2-obtained in Example 1-2
(5-chloro-1H-indole-2-carbonyl)-
Hydrazide (87.1 mg) was suspended in formic acid (3 ml), the temperature was raised to 120 ° C., and the mixture was stirred for 6 hours. The reaction mixture was allowed to cool to room temperature, water (30 ml) was added, and the mixture was extracted with ethyl acetate-THF (1: 1) (50 ml). The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution (30 ml) and saturated aqueous sodium chloride solution (30 ml), dried and concentrated under reduced pressure. The obtained solid was slurry-washed with MeOH to give the title compound (65 mg, yield 72%) as a colorless solid (see Table 19).

Example 2-6 5-Chloro-1H-indole-2-carboxylic acid (4
-Oxo-1,4-dihydro-2H-quinazoline-3-
Yl) -amide 5-chloro-1H-indole-2-carboxylic acid (4-oxo-4H-quinazoline-3 obtained in Example 2-5
-Yl) -amide (44 mg) in THF-MeOH
It was dissolved in (1: 1) (16 ml). Acetic acid (0.4 ml) and sodium cyanoborohydride (14 ml) were added to this solution.
5 mg) were added sequentially, the temperature was raised to 85 ° C., and the mixture was stirred for 42 hours. Water (30 ml) was added to the reaction mixture, and ethyl acetate-
It was extracted with THF (1: 1) (80 ml). The organic layer was washed with saturated aqueous sodium chloride solution (30 ml), dried and concentrated under reduced pressure. The obtained solid was slurry-washed with ether to give the title compound (42 mg, yield 94%) as a colorless solid (see Table 19).

Example 2-7 5-Chloro-1H-indole-2-carboxylic acid
(2,5-dioxo-1,2,3,5-tetrahydro-
Benzo [e] [1,4] diazepin-4-yl) -amide 2-amino-benzoic acid 2-obtained in Example 1-2
(5-chloro-1H-indole-2-carbonyl)-
The hydrazide (203 mg) was dissolved in THF (25 ml). Pyridine (0.28 ml) was added to this solution, and 0
After cooling to ℃, acetyl chloride (0.054m
l) was added. The reaction solution was heated to room temperature and stirred for 12 hours and 30 minutes. After adding water (50 ml) to the reaction mixture, T
It was extracted with HF-ethyl acetate (1: 1) (100 ml). The organic layer was 10% aqueous citric acid solution (30 ml), water (30 ml), saturated aqueous sodium chloride solution (30 ml).
The extract was washed successively with, dried, and concentrated under reduced pressure. The obtained solid was slurry-washed with ether. This solid was added to DMF (7 m
It was dissolved in 1). Potassium carbonate (225m
g) and sodium iodide (catalyst amount) were added sequentially,
The temperature was raised to and the mixture was stirred for 2 hours. The reaction mixture was allowed to cool to room temperature, water (30 ml) was added, and the mixture was extracted with THF-ethyl acetate (1: 1) (100 ml). The organic layer was washed with saturated aqueous sodium chloride solution (30 ml), dried and concentrated under reduced pressure. The resulting solid is slurry washed with THF,
The title compound (117 mg, 67% yield) was obtained as a colorless solid (see Table 19).

Example 2-8 5-Chloro-1H-indole-2-carboxylic acid
(2,5-Dioxo-2,3-dihydro-5H-benzo [e] [1,4] oxazepin-4-yl) -amide 2- (carboxymethyl) hydroxy-benzoic acid 2-
(5-Chloro-1H-indole-2-carbonyl) hydrazide (131 mg), HOBt.H ₂ O (85 m
g) was dissolved in DMF (2.5 ml) and then EDC (8
5 mg) was added and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with THF-ethyl acetate (1: 1) (80 ml), water (30 ml), 10% aqueous citric acid solution (30 m).
l), water (30 ml), saturated aqueous sodium chloride solution (3
It was washed successively with 0 ml). The solution was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The obtained solid was slurry-washed with ether to give the title compound (89 mg, yield 58%) as a colorless solid (see Table 19).

Examples 2-9 to 2-31 Examples 2-9 to 2-3 are carried out in the same manner as Examples 2 to 2-8.
1 compound was obtained. The obtained compounds are shown in Tables 19 to 22.

[0137]

[Table 19]

[0138]

[Table 20]

[0139]

[Table 21]

[0140]

[Table 22]

Example 3 N- (2,4-dioxo-perhydropyrimidine-3-
Yl) -5-chloro-1H-indole-2-carboxamide a) {3- [2- (5-chloro-1H-indole-2
-Carbonyl) hydrazino] -3-oxopropyl} carbamic acid tert-butyl ester By using N- (tert-butoxycarbonyl) -β-alanine instead of anthranilic acid in the same manner as in Example 1-2, the title was obtained. A compound (yield 48%) was obtained. ¹ H-NMR (δ value, 300 MHz, DMSO-
d _6). 1.39 (9H, s), 2.37 (2H, t, J = 7.
5Hz), 3.19 (2H, m), 6.81 (1H,
m), 7.19-7.23 (2H, m), 7.45 (1
H, d, J = 8.7 Hz), 7.73 (1 H, m),
9.97 (1H, brs), 11.83 (1H, s).

B) N- (2,4-dioxo-perhydropyrimidin-3-yl) -5-chloro-1H-indole-2-carboxamide obtained in Example 3 a) {3- [2- (5-chloro-
1H-indole-2-carbonyl) hydrazino] -3
-Oxopropyl} carbamic acid tert-butyl ester (577 mg) was added to trifluoroacetic acid (6
ml). When trifluoroacetic acid was distilled off under reduced pressure, a solid residue was obtained. This residue was dissolved in THF (3 ml) and triethylamine (0.31 ml) was added.
Carbonyldiimidazole (357 mg) was added to this solution, and the mixture was stirred at room temperature for 1 day and at 50 ° C. for 1 hour. The reaction solvent was evaporated under reduced pressure, and the obtained residue was dissolved in ethyl acetate.
This solution was washed successively with water, hydrochloric acid (0.5N), saturated aqueous sodium hydrogen carbonate and water. The solution was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure and the residue was crystallized from ethyl acetate and diethyl ether to give the title compound (80 mg, yield 12%) as white crystals (see Table 23).

Example 3-2 N- (4-oxo-2-thioxo-perhydropyrimidin-3-yl) -5-chloro-1H-indole-2-
Carboxamide The title compound (74% yield) was obtained as in Example 3b), but using thiocarbonyldiimidazole instead of carbonyldiimidazole (Table 23).
reference).

Example 3-3 N- (2,4-dioxo-1-phenyl-perhydropyrimidin-3-yl) -5-chloro-1H-indole-2-carboxamide a) 3-anilinopropionate aniline A solution of (5.00 g) in acetonitrile (30 m
β-Propiolactone (3.36 ml) was added dropwise to the mixture obtained by heating under 1). After heating under reflux for 3 hours,
The solvent was evaporated under reduced pressure, and the residue was dissolved in aqueous sodium hydroxide solution. The mixture was washed with diethyl ether, adjusted to pH 4-5 with hydrochloric acid, and extracted with diethyl ether. The organic layer was washed with water and saturated saline and dried over sodium sulfate. This was filtered and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (chloroform: MeO).
The product was purified with H = 9: 1) to obtain 3-anilinopropionic acid (2.08 g, yield 23%).

B) 5-chloro-1H-indole-2
-Carboxylic acid 2- (3-anilinopropionyl) hydrazide 5-chloro-1H-indole-2-carboxylic acid obtained in Example 1 a) Obtained with hydrazide (419 mg) and Example 3-3 a). Of compound 3 (330 mg)
To the MF suspension (10 ml) was added 1-hydroxybenzotriazole (368 mg) and EDC (460 mg). After stirring at room temperature for 12 hours, water was added to the reaction solution. The mixture was extracted with ethyl acetate and the organic layer was extracted with 10
% Aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine in that order, and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure, and the residue was washed with ethyl acetate.
The crystals were recrystallized from -hexane to give the title compound (468 mg, yield 66%).

C) N- (2,4-dioxo-1-phenyl-perhydropyrimidin-3-yl) -5-chloro-
1H-indole-2-carboxamide 5-chloro-1H-indole-2-carboxylic acid obtained in Example 3-3 b) 2- (3-anilinopropionyl) hydrazide (51.0 mg) in THF ( 3m
To l) was added triethylamine (44 mg) and triphosgene (15.6 mg). After stirring at room temperature for 4 hours,
Water was added. This mixture was extracted with ethyl acetate, and the organic layer was mixed with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution,
It was washed with saturated saline and dried over sodium sulfate. This was filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 1: 2) to give the title compound (34 mg, yield 62%) (see Table 23).

Example 3-4 N- (4-oxo-1-phenyl-perhydropyrimidin-3-yl) -5-chloro-1H-indole-2-
Carboxamide 5-chloro-1H-indole-2-carboxylic acid 2- (3-anilinopropionyl) hydrazide obtained in b) of Example 3-3 (100 mg) in ethanol (5 m
l) Paraformaldehyde (68 mg) was added to the suspension. After stirring at room temperature for 7 days, water was added. The mixture was extracted with ethyl acetate, the organic layer was washed with saturated brine and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform: MeOH = 20: 1) to give the title compound (48
mg) was obtained (see Table 23).

Examples 3-5 to 3-15 In the same manner as Examples 3 to 3-4, Examples 3-5 to 3-1.
5 compound was obtained. The obtained compounds are shown in Tables 23 to 24.

[0149]

[Table 23]

[0150]

[Table 24]

Example 4 N- (2,4-dioxo-5-phenylimidazolidin-3-yl) -5-chloro-1H-indole-2-carboxamide a) {2- [2- (5-chloro- 1H-Indole-2
-Carbonyl) hydrazino] -2-oxo-1-phenyl-ethyl} -carbamic acid tert-butyl ester and 5-chloro-1H-indole-2-carboxylic acid hydrazide obtained in Example 1 a) (420 mg) 2-
Suspension of (tert-butoxycarbonylamino) -2-phenylacetic acid (503 mg) in DMF (10 ml)
And 1-hydroxybenzotriazole monohydrate (36
8 mg) and EDC (460 mg) were added. After stirring this reaction solution at room temperature for 14 hours, water was added to the reaction solution.
The reaction solution was extracted with ethyl acetate, and the organic layer was washed successively with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, and dried over sodium sulfate. This solution was filtered and concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate / n-hexane to give the title compound (790 mg, yield 89%).
Got

B) 5-chloro-1H-indole-2
-Carboxylic acid 2-((α-aminobenzyl) carbonyl) hydrazide 2- [2- (5-chloro-1) obtained in a) of Example 4
H-indole-2-carbonyl) hydrazino] -2-
Oxo-1-phenyl-ethyl} -carbamic acid te
To a suspension of rt-butyl ester (500 mg) in dichloromethane (5 ml) was added trifluoroacetic acid (5 m) at room temperature.
l) Added. The reaction solution was stirred at room temperature for 5 hours, and aqueous sodium hydrogen carbonate was added to make the solution alkaline. This mixture was extracted with ethyl acetate, the organic layer was washed with water and saturated brine, and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate / n-hexane to give the title compound (366 mg, yield 94%).
Got ¹ H-NMR (σ) ppm (300 MHz, DMSO-
_{d 6) 4.54 (1H, s} ), 7.19-7.37 (5H,
m), 7.44 (1H, d, J = 8.7 Hz), 7.5
4 (2H, d, J = 7.5Hz), 7.71 (1H,
d, J = 1.8 Hz), 11.91 (1H, s).

C) N- (2,4-dioxo-5-phenylimidazolidin-3-yl) -5-chloro-1H-indole-2-carboxamide 5-chloro-obtained in Example 4b). 1H-indole-2-carboxylic acid 2-((α-aminobenzyl) carbonyl) hydrazide (80.0 mg) in THF (3
carbonyldiimidazole (45.8 ml) at room temperature.
mg) was added. After stirring at room temperature for 16 hours, a 10% aqueous citric acid solution was added. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline and dried over sodium sulfate. This was filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 2) to give the title compound (75 mg, yield 8
7%) (see Table 25).

Example 4-2 N- (2,4-dioxo-1-phenylimidazolidin-3-yl) -5-chloro-1H-indole-2-carboxamide a) 5-chloro-1H-indole-2 -Carboxylic acid
2- (anilinoacetyl) hydrazide To the DMF suspension (5 ml) of 5-chloro-1H-indole-2-carboxylic acid hydrazide (210 mg) obtained in Example 1 a) and anilinoacetic acid (151 mg), 1
-Hydroxybenzotriazole (184g) and EDC
(230 mg) was added. After stirring at room temperature for 13 hours,
Water was added to the reaction solution. This mixture was extracted with ethyl acetate, and the organic layer was washed with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine in that order, and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate-n-hexane to give the title compound (321 mg, yield 94%).

B) N- (2,4-dioxo-1-phenylimidazolidin-3-yl) -5-chloro-1H-indole-2-carboxamide obtained in Example 4-2 a). Chloro-1H-indole-2-carboxylic acid 2- (anilinoacetyl) hydrazide (203 mg) in THF (10 ml)
Carbonyldiimidazole (140 mg) was added to. After stirring at 60 ° C. for 13 hours, the mixture was allowed to cool and 10% citric acid aqueous solution was added. The mixture was extracted with ethyl acetate, the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over sodium sulfate. This was filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1), and the title compound (2
1 mg, yield 10%) was obtained (see Table 25).

Example 4-3 N- (4-oxo-1-phenyl-2-thioxoimidazolidin-3-yl) -5-chloro-1H-indole-2-carboxamide b of Example 4-2) In a similar manner, but using thiocarbonyldiimidazole instead of carbonyldiimidazole, the title compound was obtained (see Table 25).

Example 4-4 N- (1-oxo-4-phenylimidazolidine-2-
Yl) -5-chloro-1H-indole-2-carboxamide of 5-chloro-1H-indole-2-carboxylic acid 2- (anilinoacetyl) hydrazide (103 mg) obtained in a) of Example 4-2. Paraformaldehyde (36 mg) was added to an ethanol (3 ml) suspension. After stirring at room temperature for 5 days, water was added. The mixture was extracted with ethyl acetate, the organic layer was washed with saturated brine and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give the title compound (7
3 mg, yield 69%) was obtained (see Table 25).

Example 4-5 N- (2-oxo-1-phenylimidazolidine-3-
Yl) -5-chloro-1H-indole-2-carboxamide a) 1- (5-chloro-1H-indole-2-carbonyl) -4-phenylsemicarbazide 5-chloro-obtained in a) of Example 1 1H-indole-2-carboxylic acid hydrazide (800 mg) in THF
(10 ml) suspension, phenyl isocyanate (47
7 mg) was added. After stirring at room temperature for 2 hours, diethyl ether was added. The precipitated solid was collected by filtration and dried under reduced pressure to give the title compound (1.24 g, yield 99%).

B) N- (2-oxo-1-phenylimidazolidin-3-yl) -5-chloro-1H-indole-2-carboxamide 1- (5 obtained in a) of Example 4-5. -Chloro-1H
-Indole-2-carbonyl) -4-phenylsemicarbazide (100 mg) in DMF (5 ml),
1,2-Dibromoethane (63 mg) and potassium carbonate (92 mg) were added. After stirring at 60 ° C. for 18 hours, the mixture was allowed to cool and 10% aqueous citric acid solution was added. Extracted with ethyl acetate, the organic layer was saturated aqueous sodium hydrogen carbonate, water,
It was washed with saturated saline and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane: ethyl acetate = 2:
Purification in 1) gave the title compound (45 mg, 42% yield) (see Table 25).

Examples 4-6 to 4-20 Examples 4-6 to 4-2 are carried out in the same manner as Examples 4 to 4-5.
0 compound was obtained. The obtained compounds are shown in Tables 25 to 27.

[0161]

[Table 25]

[0162]

[Table 26]

[0163]

[Table 27]

Example 5 1- (5-Chloro-1H-indole-2-carbonyl) -4-phenylsemicarbazide 5-chloro-1H-indole-2-carboxylic acid hydrazide obtained in Example 1 a) 105 mg) and phenyl isocyanate (54 μl) in dioxane (1 ml)
The reaction was carried out for 1 hour. THF (5 ml) was added to the reaction solution, and the mixture was heated at 60 ° C. for 1 hour. The reaction solution is concentrated,
Crystals precipitated upon standing. This was collected by filtration and dried under reduced pressure to give the title compound (144 mg, yield 88%) (see Table 28).

Example 5-2 5-Chloro-1H-indole-2-carboxylic acid 2-
(Phenylthio) carbonyl hydrazide The title compound (23% yield) was obtained in the same manner as in Example 5-1, except that phenylisothiocyanate was used instead of phenylisocyanate (see Table 28).

Example 5-3 5-Chloro-1H-indole-2-carboxylic acid 2-
Phenylacetyl hydrazide 5-chloro-1H-indole-2-carboxylic acid hydrazide (91.1 mg) obtained in a) of Example 1 was added to TH.
It was suspended in F, triethylamine (0.05 ml) and phenylacetyl chloride (0.065 ml) were sequentially added, and the mixture was stirred at room temperature for 1 hour and 30 minutes. Water (2 ml) and sodium hydrogen carbonate (34 mg) were sequentially added to the reaction mixture, and the mixture was stirred for 1 hr, and the precipitated solid was collected by filtration to give the title compound (112 mg, yield 79%) as a colorless solid. (See Table 28).

Example 5-4 5-Chloro-1H-indole-2-carboxylic acid 2-
(Benzoylformyl) hydrazide To the DMF suspension (5 ml) of 5-chloro-1H-indole-2-carboxylic acid hydrazide (240 mg) obtained in Example 1 a) and benzoylformic acid (150 mg) was added.
1-Hydroxybenzotriazole (184 mg) and EDC (230 mg) were added. After stirring at room temperature for 14 hours, water was added to the reaction solution. This mixture was extracted with ethyl acetate, and the organic layer was washed successively with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, and dried over sodium sulfate. The solution was filtered, concentrated under reduced pressure, and the residue was washed with diethyl ether to give the title compound (106 mg) (see Table 28).

Examples 5-5 to 5-19 Examples 5-5 to 5-1 are carried out in the same manner as Examples 5 to 5-4.
9 compounds were obtained. The obtained compounds are shown in Tables 28 to 30.

[0169]

[Table 28]

[0170]

[Table 29]

[0171]

[Table 30]

Example 6 5-Chloro-1H-indole-2-carboxylic acid 2-
(Imino-phenyl-methyl) hydrazide hydrochloride 5-chloro-1H-indole-2-carboxylic acid 2- (imino-phenyl-methyl) obtained in Examples 1-7
Hydrazide (35.6g) in MeOH (530m)
1) under ice cooling, a 4N hydrochloric acid / ethyl acetate solution (34.2) was added.
ml) was added dropwise. After stirring at room temperature for 1 hour, diisopropyl ether was added to this reaction solution. The precipitated crystals were collected by filtration and washed with diisoproprether. This was dried under reduced pressure to give the title compound (30.3 g, yield 76%) (see Table 31).

Example 6-2 2-Amino-4,5-difluorobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide benzenesulfonate 2-amino-4,5-difluorobenzoic acid 2- (5-methyl-1H-indole-obtained in Example 1-67
2-Carbonyl) hydrazide (67.6 mg) and benzenesulfonic acid monohydrate (51.2 mg) in THF
(1.0 ml) was heated at 60 ° C. to give a solution. When this solution was allowed to stand at room temperature for 2 hours, crystals began to precipitate. The crystals were separated, washed with THF, and dried under reduced pressure to give the title compound (83.3 mg, yield 85%) as pale-yellow needle crystals (see Table 31).

Example 6-3 2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide benzenesulfonate Obtained by a method similar to that of Example 1-97. 2-amino-4
-Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide (694.0 mg)
And benzenesulfonic acid monohydrate (475.0 mg) were heated in methanol (70 ml) at 65 ° C. to give a solution. When this solution was concentrated to about 10 ml, crystals began to precipitate. The crystals were separated, washed with methanol, and dried under reduced pressure to give the title compound (900.0 mg, 89%) as colorless needle crystals (see Table 31).

Example 6-4 3- (Dimethylamino) benzoic acid 2- (5-chloro-)
1H-indole-2-carbonyl) hydrazide methanesulfonate 3- (dimethylamino) benzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide obtained in Example 1-45 (68.3 mg) ) And methanesulfonic acid (19 μl) were dissolved in methanol (0.7 ml) at room temperature. Diethyl ether (1.0 m
When l) was dropped, needle-like crystals were precipitated. The crystals were separated, washed with diethyl ether, and dried under reduced pressure to give the title compound (72.8 mg, 84%) as colorless needle crystals (see Table 31).

Example 6-5 2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide hydrochloride 2-amino-4-obtained in Example 1-97 Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide (93 mg) was added to methanol (7.
0 ml). A 4N hydrochloric acid-dioxane solution (0.55 ml) was added to this mixture, and the mixture was heated to 60 ° C to obtain a solution. Diethyl ether (5 ml) was added dropwise to the resulting solution. When the obtained mixture was left for 1 hour, white crystals were obtained. The precipitated crystals were filtered and washed with methanol. This was dried under reduced pressure to give the title compound (670 mg, 8
7%) as colorless needles (see Table 31).

Example 6-6 2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p
-Toluenesulfonic acid salt 2-amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide (693 mg) obtained in Example 1-97 and p-toluenesulfonic acid monohydrate The Japanese product (571 mg) was added to DMSO (2.
5 ml). The resulting solution was added dropwise to methanol (6 ml) with stirring over 3 minutes. The precipitated crystals were filtered and washed with methanol. This was dried under reduced pressure to give the title compound (897 mg, 86%) as colorless needle crystals (see Table 31).

Example 6-7 2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p
- The obtained toluene sulfonate Example 1-97 2-Amino-4-fluorobenzoic acid 2- (5-chloro -1H- indole-2-carbonyl) hydrazide (1.73g) _{THF: H} 2 O
It was dissolved in a mixed solvent (10: 1) (10: 1). p-Toluenesulfonic acid monohydrate (1.05 g) was added to THF (1
ml) and heated to 60 ° C. 2-amino-4-
Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide in a water-containing THF solution was added to p.
-Drop to a toluene solution of toluenesulfonic acid at 60 ° C. After the dropping was completed, the mixture was stirred at room temperature for 3 hours.
The precipitated crystals were collected by filtration and washed with THF. The crystals were dried under reduced pressure to give the title compound (1.99 g, 77%) as colorless needle crystals (see Table 31).

Example 6-8 2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p
-Toluenesulfonic acid salt 2-amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide (5.00 g) obtained in Example 1-97 was added to THF: methanol: H. ₂ O (70:30:10) mixed solution (47.5 m
It was dissolved in 1) at 60 ° C. While stirring, p-
A THF: methanol: H ₂ O (70:30:10) mixture (4.1 ml) of toluenesulfonic acid (4.11 g) was added dropwise over 5 minutes while maintaining 60 ° C. After the dropping was completed, the mixture was stirred at room temperature for 3 hours. The precipitated crystals were treated in the same manner as in Example 1 to give the title compound (6.42 g, 86
%) As colorless needles (see Table 31).

Example 6-9 2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p
-Toluenesulfonic acid salt 2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide (347 mg) obtained in Example 1-97 and p-toluenesulfonic acid monohydrate The Japanese product (190 mg) was suspended in n-hexane (15 ml). The mixture was stirred at room temperature for 1 week. The obtained crystals were collected by filtration and washed with n-hexane. The crystals were dried under reduced pressure to give the title compound (430 mg,
83%) was obtained as a white powder (see Table 32).

Example 6-10 2-Aminobenzoic acid 2- (5-Methyl-1H-indole-2-carbonyl) hydrazide p-toluenesulfonic acid salt Using the compound obtained in Example 1-62 as a starting material ,
Prepared by the method of Examples 6-8 (see Table 32).

Example 6-11 2-Aminobenzoic acid 2- (5-Methyl-1H-indole-2-carbonyl) hydrazide benzene sulfonate Using the compound obtained in Example 1-62 as a starting material,
Prepared by the method of Example 6-2 (see Table 32).

Example 6-12 2-Amino-4-fluorobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide benzene sulfonate As a raw material, the compound obtained in Example 1-63 was used. make use of,
Prepared by the method of Example 6-2 (see Table 32).

Example 6-13 3-Aminobenzoic acid 2- (5-Methyl-1H-indole-2-carbonyl) hydrazide p-toluenesulfonic acid salt The compound obtained in Example 1-142 was used as a starting material. Manufactured by the method of Examples 6-8 (see Table 32).

Examples 6-14 to 6-35 Examples 6-14 to 6 were carried out in the same manner as Examples 6 to 6-13.
The compound of -35 was obtained. The obtained compounds are shown in Tables 31 to 35.
It was shown to.

[0186]

[Table 31]

[0187]

[Table 32]

[0188]

[Table 33]

[0189]

[Table 34]

[0190]

[Table 35]

Pharmacological Test Test Example (1) Method for Measuring Liver Glycogen Phosphorylase Activity Glycogen phosphorylase activity is measured by the reverse reaction, that is, the concentration of phosphate produced in the reaction in which glycogen phosphorylase synthesizes G1-P into glycogen. It was done by doing. As an enzyme solution of human liver glycogen phosphorylase, a cell lysate of Sf9 cells forcibly expressing recombinant human liver glycogen phosphorylase was treated with 1 mM imidazole-hydrochloric acid buffer solution (pH 7.0,
0.2 mM PMSF, 250 mM NaCl, 0.02
A protein diluted to 80 μg / mL with 5% BSA was used. As a substrate solution, 25 mM Tris-H
Cl buffer (pH 7.2, 250 mM KCl, 6.2)
5 mM MgCl ₂ , 6.25 mM EGTA, 1.2
5 mM glucose-1-phosphate,
2.5 mg / ml glycogen, 7.5 mM g
lucose-containing) was used. The test drug was dissolved in 0.5% dimethyl sulfoxide (DMSO). Study drug 10
The enzyme reaction was started by adding 20 μl of the enzyme solution to a mixed solution of μl and 20 μl of the substrate solution. As a control, 0.5% DMSO was added instead of the test drug. A blank containing no enzyme was used. After reacting for 60 minutes at room temperature, 50 μl of malachite green solution was added, and after reacting for 20 minutes at room temperature, the absorbance at 650 nm was measured. The enzyme solution was added to the blank at the same time as the malachite green solution, and the same measurement was performed. Inhibition rate of test drug (%)
Was calculated by ((value of control-value of test drug) / (control value-blank value)) x 100 (%). The test results of the above test examples are shown in Tables 36 to 38.

[0192]

[Table 36]

[0193]

[Table 37]

[0194]

[Table 38]

Test (2) Method for Measuring Plasma Glucose Concentration The effect of the compound (1) of the present invention on plasma glucose concentration was examined using obesity-type diabetes model db / db mice. The glucose concentration in plasma of db / db mice (10 to 15 weeks old) was measured, and the mice were divided into 5 groups so that there was no difference in the average value of the glucose concentration in plasma of each group.
After fasting for 4 hours, the test drug or solvent (0.5% methylcellulose) was orally administered to db / db mice, and plasma glucose concentrations were measured 1 and 3 hours after administration. The hypoglycemic effect of the test drug was evaluated by performing a significant difference test between the vehicle administration group and the test drug administration group at each time (D).
unnett test). The test results of the above test examples are shown in Table 39.

[0196]

[Table 39]

[0197]

As is apparent from the above test, the novel compound of the present invention and its pharmaceutically acceptable salt strongly inhibited human liver glycogen phosphorylase. Since it has such an action mechanism, the compound (1) of the present invention is useful as a therapeutic drug for diabetes. In addition, the compound of the present invention is useful in combination with other therapeutic agents for diabetes or hyperlipidemia.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/4178 A61K 31/4178 4C204 31/4188 31/4188 31/4196 31/4196 31/427 31/427 31/4439 31/4439 31/455 31/455 31/497 31/497 31/513 31/513 31/517 31/517 31/536 31/536 31/5377 31/5377 31/5513 31/5513 31 / 553 31/553 45/00 45/00 A61P 3/06 A61P 3/06 3/10 3/10 43/00 111 43/00 111 123 123 123 C07D 401/12 C07D 401/12 401/14 401/14 403 / 12 403/12 405/12 405/12 409/12 409/12 409/14 409/14 413/12 413/12 417/12 417/12 487/04 138 487/04 138 495/04 103 103 495/04 103 (72) Inventor Junhisa Ueda 1-1, Murasaki-cho, Takatsuki-shi, Osaka F-Term (Reference), Pharmaceutical Research Institute, Japan Tobacco Inc. 4C050 AA01 BB05 CC04 EE02 FF01 GG03 HH04 4C063 AA01 AA03 BB09 CC12 CC22 CC23 CC25 CC29 CC31 CC34 CC37 CC47 CC54 CC57 CC62 CC75 CC92 DD06 EE01 4C071 AA01 BB01 CC01 CC21 DD02 DD04 EE13 FF03 HH28 JJ05 BCLLA 4C084 A13A86A48A36A02 ZC332 ZC202 ZC332 ZC332 ZC332 ZC332 ZC332 ZC332 ZC332 ZC332 ZC332 ZC332 BC56 BC60 BC62 BC72 BC73 BC75 BC82 CB03 CB27 GA02 GA03 GA06 GA08 GA09 GA10 GA12 MA01 MA02 MA04 NA14 NA15 ZC20 ZC35 4C204 BB01 CB03 DB26 EB02 FB01 GB02 GB24

Claims (20)

[Claims] 1. The general formula (1) [Chemical 1] [In the formula, R¹Is a hydrogen atom, C_1-6Alkyl group or
Is a silyl group; R^TwoIs a hydrogen atom or a halogen atom
R; R^ThreeIs a halogen atom, C_1-6Alkyl group, C
_1-6Alkoxy group, nitro group, amino group, hydroxyl group,
Ano group, acyl group, aralkyloxy group or thiazolyl
A group (the thiazolyl group is C_1-6Alkyl group or amino
R may be substituted with a group); R^FourIs a hydrogen atom or
C_1-6An alkyl group; R⁵Is a hydrogen atom, C
_1-6Alkyl group or C_2-7Alkoxycarbonyl group
And R⁶Is a hydrogen atom, C_1-6Alkyl group or
Aralkyl group (the aralkyl group is substituted with a halogen atom)
R); R⁷Is [Chemical 2] {Where X is = O, = S or = NH; A is
-N (R⁸)-(Where R⁸Is a hydrogen atom, C_1-6A
Alkyl group or an aryl group which may have a substituent.
, -C (R⁹) (R¹⁰)-(Where R⁹And R
¹⁰Are the same or different and independently,
Group, amino group, C_1-6Alkyl group, C_1-6Hydroxy
Sialkyl group, C_2-7Alkoxycarbonylamino group
Or an acylamino group, or R⁹And R¹⁰
Together with the adjacent carbon atom, C_3-7Cycloa
An alkyl group may be formed),-(CH_Two)_m-NH-
(Where m is an integer of 1 to 4), -CO-, -S.
-Or a single bond; B is [Chemical 3] (Where R¹¹, R¹², R^Thirteen, R¹⁴Or R¹⁵
Are the same or different, independently, a hydrogen atom, a halogen
Atom, C_1-6Alkyl group, C_1-6Alkoxy group, d
Toro group, hydroxyl group, cyano group, haloalkyl group, aralkyl
Group, aryl group which may have a substituent, aryl
Oxy group, tetrazolyl group, triazolyl group,-(CH
_Two)_p-CO-R¹⁹(Where p is an integer of 0 or 1 to 4
Is a number, R¹⁹Is an aryl which may have a substituent
Group, hydroxyl group, C_1-6Alkoxy group or -N (R²⁰)
(R²¹)-(Where R²⁰And R²¹Are the same or
Differently, independently, hydrogen atom, C_1-6An alkyl group,
Aralkyl group or C_3-13Alkoxy carbonyl al
Kill group or R²⁰And R²¹Adjacent to
Together with elementary atoms, [Chemical 4] (Here, q is an integer of 1 to 3, and R²²Is hydrogen
Child, hydroxyl group, C_1-6Alkoxy group, amino group, C
_2-12Dialkylamino group or C_2-7Alkoxyca
May be a carbonyl group).
), -O- (CH_Two)_r-R²³(Where r is 1 to
R is an integer of 4²³Is hydroxyl group, amino group, C_{2- 7}
Alkylcarbonyloxy group or -CO-R²⁴(here
And R²⁴Is a hydroxyl group, C_1-6Alkoxy group or -N
(R²⁵) (R²⁶)-(Where R²⁵And R
²⁶Are the same or different and are a hydrogen atom, C_1-6Archi
R or aralkyl, or R²⁵And R
²⁶Together with the adjacent nitrogen atom, [Chemical 5] (Where q'and R^{22 '}Are q and R respectively²²When
Synonyms) may be formed))),-
O-CO-R²⁷(Where R²⁷Is C_1-6Alkyl
Amino group or C_2-12A dialkylamino group),
Or -N (R²⁸) (R²⁹) (Where R²⁸And R
²⁹Are the same or different and are a hydrogen atom, C _1-6Archi
Group, aryl group which may have a substituent, acyl
Group,-(CH _Two)_{p '}-COO-R^Thirty(Where p ’
Is synonymous with p and R^ThirtyHas a hydrogen atom and a substituent
Optionally an aryl group or C_1-6Alkyl group (the C
_1-6The alkyl group is a hydroxyl group, a trifluoromethyl group,
An optionally substituted aryl group, morpholino group or
Is optionally substituted with a carboxyl group), -C
ON (R³¹) (R³²) (Where R³¹And R³²
Are the same or different and are a hydrogen atom, C_1-6Alkyl group
Or an aryl group which may have a substituent),
CO-R³³(Where R³³Is C_1-6Alkyl group
Is an aryl group which may have a substituent), -C
O- (CH_Two)_{r '}-R³⁴(Where r'is synonymous with r
And R³⁴Is C_1-6Alkylamino group, C
_2-12Dialkylamino group, C_1-6Alkoxy group
Is C_2-7Is an alkylcarbonyloxy group)
R) and R^16b~ R¹⁶ⁿAnd R^17b~ R
¹⁷ⁿAre the same or different and are a hydrogen atom, a halogen atom,
C_1-6Alkyl group, amino group, hydroxyl group, C_1-6Al
Coxy group or -CON (R^{31 '}) (R^{32 '})(here
And R^{31 '}And R^{32 '}Is R³¹And R³²Synonymous with
Yes, and R¹⁸Is a hydrogen atom or C_2-7Arcoki
Is a carbonyl group, and Y is -S-, -O- or -N.
(R³⁵)-(Where R³⁵Is a hydrogen atom or C_{1 -6}
Is an alkyl group), and n is 0 or an integer of 1 to 4.
Is)} or R⁶And R⁷Adjacent to
Together with the nitrogen atom [Chemical 6] {Where R³⁶And R³⁷Are the same or different,
Elementary atom, halogen atom, C_1-6Alkyl group, C_1-6
Alkoxy group, amino group, nitro group, hydroxyl group, C _2-7
Alkoxycarbonyl group, carboxyl group, C_2-7Ha
Roalkylcarbonylamino group or -O-CO-R⁴¹
(Where R⁴¹Is C_1-6Alkyl group, C_1-6A
Rukylamino group or C_2-12Is a dialkylamino group
Z) is -CH_Two-CH_Two-, -C
(R⁴²) = CH-, -C (R^{42 '}) = N−, −N =
N-, -CO-, -CO-O-, -CO-CH_Two-O
-, -CH_Two-CO-NH-, -C (R^{42 ''}) (R
⁴³) -N (R⁴⁴)-(Where R⁴², R^{42 '},
R^{42 ''}And R⁴³Are the same or different hydrogen atoms,
C_1-6Ali which may have an alkyl group or a substituent
Group, and R⁴⁴Is a hydrogen atom, C_1-6Alkyl
Group (the C_1-6The alkyl group is a carboxyl group or C
_2-7(May be substituted with an alkoxycarbonyl group)
Is C_2-7An alkoxycarbonyl group) or -C
(U) -N (R^{44 '})-(Where U is = O or = S
And R^{44 '}Is R⁴⁴(Synonymous with)
And each group is a group adjacent to the nitrogen atom on the fused ring of formula (i).
Children are listed on the left edge); R³⁸Is a hydrogen atom, a substituent
An aryl group or a heteroaryl group which may have
R; R³⁹And R⁴⁰Are the same or different and
Child, C_1-6Alkyl group, C_{1 -6}Alkoxy group or C
_2-7An alkoxycarbonyl group or R^Three
9And R⁴⁰Together with the adjacent carbon atom, [Chemical 7] W may be formed; W is -CO-, -CS- or -CH
_Two-Is; V₁Is -CO-, -CS- or -CH_Two−
And V_TwoIs -O-, -CH_Two-Or-N (R⁴⁵)
-(Where R⁴⁵Is a hydrogen atom, C_1-6Alkyl group
Or an aryl group which may have a substituent).
R; V_ThreeIs -CH (R⁴⁶)-Or -N (R^{46 '}) −
(Where R⁴⁶And R^{Four 6 '}Is the hydrogen source
Having a child, an aralkyl group, a heteroaryl group or a substituent
Is an optionally substituted aryl group).
Indole compound represented by
Obtained salt or prodrug. 2. R⁶Is a hydrogen atom, C_1-6Alkyl group
Or an aralkyl group (the aralkyl group is a halogen atom
R may be substituted); R⁷But, [Chemical 8] {Where X is = O, = S or = NH; A is
-N (R^{8 '})-(Where R^{8 '}Is a hydrogen atom, C
_1-6Phenyl which may have an alkyl group or a substituent
Group), -C (R^{9 '}) (R^{10 '})-(Here
And R^{9 '}And R^{10 '}Are the same or different and
Child, hydroxyl group, amino group, C_1-6Alkyl group, C_1-6
Hydroxyalkyl group, C_2-7Alkoxy carbonyl
An amino group or an acylamino group, or R^{9 '}
And R^{10 '}Together with the adjacent carbon atom, C
_3-7A cycloalkyl group may be formed),-(CH
_Two)_m-NH- (where m is an integer from 1 to 4),
-CO-, -S- or a single bond; B is [Chemical 9] (Where R^{11 '}, R^{12 '}, R^{13 '}, R^{14 '}or
Is R^{15 '}Are the same or different and are hydrogen atom, halogen
Atom, C_1-6Alkyl group, C_1-6Alkoxy group, d
Toro group, hydroxyl group, cyano group, haloalkyl group, aralkyl
Group, optionally substituted phenyl group, aryl
Oxy group, tetrazolyl group, triazolyl group,-(CH
_Two)_p-CO-R^{19 '}(Where p is 0 or 1 to 4
Is an integer, R^{19 '}Is a group which may have a substituent
Nyl group, hydroxyl group, C_1-6Alkoxy group or -N (R
²⁰) (R²¹)-(Where R²⁰And R²¹Is billed
(Synonymous with item 1)), -O- (CH_Two)_r-R
²³(Where r and R²³Is synonymous with claim 1.
), -O-CO-R²⁷(Where R²⁷Is claim 1
Synonymous with), or -N (R^{28 '}) (R^{29 '})
(Where R^{28 '}And R^{29 '}Are the same or different
, Hydrogen atom, C_1-6Has an alkyl group and a substituent
Optionally a phenyl group, an acyl group,-(CH_Two)_{p '}-C
OO-R^{30 '}(Here, p'is synonymous with claim 1.
R^{30 '}Is a hydrogen atom or a group which may have a substituent.
Phenyl group or C_1-6Alkyl group (the C_1-6Alkyl
The group has a hydroxyl group, a trifluoromethyl group, and a substituent
Optional phenyl group, morpholino group or carboxyl
Group, which may be substituted with a group), -CON (R
^{31 ''}) (R^{32 ''}) (Where R^{31 ''}And R
^{32 ''}Are the same or different and are a hydrogen atom, C_1-6A
Alkyl group or a phenyl group which may have a substituent
), -CO-R^{33 '}(Where R^{33 '}Is C_1-6
An alkyl group or a phenyl group which may have a substituent
Yes), -CO- (CH_Two)_{r '}-R³⁴(here,
r'and R³⁴Is synonymous with claim 1)
Yes, R^{16b '}~ R^{16n '}And R^{17b '}~ R
^{17n '}Are the same or different and are hydrogen atom,
Child, C_1-6Alkyl group, amino group, hydroxyl group, C_1-6
Alkoxy group or -CON (R^{31 '''}) (R
^{32 '''}) (Where R^{31 '''}And R^{32 '''}
Is R^{31 ''}And R^{32 ''}Synonymous with), and R
¹⁸, Y and n are as defined in claim 1)}
Yes or R^{6 '}And R^{7 '}Are adjacent nitrogen atoms
Be with [Chemical 10] {Where R³⁶And R³⁷Is as defined in claim 1;
Z'is -CH_Two-CH_Two-, -C (R⁴²) = CH
-, -C (R^{42 '}) = N-, -N = N-, -CO-,
-CO-O-, -CO-CH_Two-O-, -CH_Two-CO
-NH-, -C (R^{42 ''}) (R⁴³) -N
(R⁴⁴)-(Where R^{Four Two}, R^{42 '}, R^{42 ''}
And R⁴³Are the same or different, a hydrogen atom, C_1-6A
Alkyl group or a phenyl group which may have a substituent
R⁴⁴Has the same meaning as in claim 1) or -C (U) -N
(R^{44 '})-(Where U and R^{44 '}Is claim 1
Synonymous with); R^{38 '}Is a hydrogen atom or,Halo
Gen atom or C_1-6Substituted with an alkyl group
Is a phenyl group or a pyridyl group; R^{39 '}as well as
R^{40 '}Are both hydrogen atoms, or R^{39 '}
And R^{40 '}Together with the adjacent carbon atom, [Chemical 11] May be formed; W and V₁Is synonymous with claim 1.
R; V_Two'Is -O-, -CH_Two-Or-N (R⁴⁵) −
(Where R⁴⁵Is a hydrogen atom, C_1-6An alkyl group,
A phenyl group which may be substituted with a halogen atom
It is; V_Three'Is -CH (R⁴⁶)-Or -N (R
^{46 '})-(Where R⁴⁶And R ^{46 '}Is that
Hydrogen atom, benzyl group, thienyl group, or halogen atom
Child, hydroxy group or C_1-6Substitute with an alkoxy group
Is a phenyl group which may be
Indole compound according to claim 1, represented by
Product, a pharmaceutically acceptable salt or prodrug thereof. 3. R⁶Is a hydrogen atom, C_1-6Alkyl group
Or an aralkyl group (the aralkyl group is a halogen atom
R may be substituted); R⁷But, [Chemical 12] {Where X is as defined in claim 1; A is -N (R
^{8 ''})-(Where R^{8 ''}Is a hydrogen atom, C_1-6A
An alkyl group or an aryl group which may have a substituent.
, -C (R^{9 ''}) (R^{10 ''})-(Where R
^{9 ''}And R^{10 ''}Are the same or different, a hydrogen atom,
Hydroxyl group, amino group, C_1-6Alkyl group, C_1-6Hide
Roxyalkyl group or C_2-7Alkoxycarbonyl
A mino group or R^{9 ''}And R^{10 ''}Next to
C together with the carbon atom that touches_3-7Cycloalk
Group may be formed),-(CH_Two)_m-NH- (
Here, m has the same meaning as in claim 1), -CO- or simple bond.
B is [Chemical 13] (Where R^{11 ''}, R^{12 ''}, R^{13 ''}, R
^{14 ''}Or R^{15 ''}Are the same or different and
Child, halogen atom, C_1-6Alkyl group, C_1-6Al
Coxy group, nitro group, hydroxyl group, cyano group, haloalkyl
Group, aralkyl group, aryl optionally having substituent (s)
Group, aryloxy group, tetrazolyl group, triazolyl
Group,-(CH_Two)_p-CO-R¹⁹(Where p and
R¹⁹Has the same meaning as in claim 1), -O- (CH_Two)_r
-R²³(Where r and R²³Is synonymous with claim 1.
Yes), -O-CO-R²⁷(Where R²⁷Is the claim
1 is synonymous with 1) or -N (R^{28 ''})
(R^{29 ''}) (Where R^{28 ''}And R
^{29 ''}Are the same or different and are a hydrogen atom, C_1-6A
Alkyl group, an aryl group which may have a substituent,
(CH_Two)_{p '}-COO-R^{30 ''}(Where p'is
synonymous with p, R^{30 ''}Is a hydrogen atom or C_1-6A
Rukiru group (the C_1-6Alkyl group is hydroxyl group, trifru
(It may be substituted with an oromethyl group or a carboxyl group)
, -CON (R³¹) (R³²) (Where R
³¹And R³²Has the same meaning as in claim 1), -CO-R
³³(Where R³³Has the same meaning as in claim 1), -C
O- (CH_Two)_{r '}-R³⁴(Where r'and R
³⁴Is synonymous with claim 1) and R
^16b~ R¹⁶ⁿAnd R^17b~ R¹⁷ⁿIs claim 1
Synonymous, R¹⁸Is synonymous with claim 1, and Y ″ is
-S- or -N (R³⁵)-(Where R³⁵Is the claim
1 is synonymous with 1), and n is synonymous with claim 1.
Or R⁶And R⁷With adjacent nitrogen atoms
Together [Chemical 14] {Where R^{36 ''}And R^{37 ''}Are the same or different
, Hydrogen atom, halogen atom, C_1-6An alkyl group,
C_1-6Alkoxy group, amino group, hydroxyl group or -OC
OR⁴¹(Where R⁴¹Is synonymous with claim 1.)
Z ″ is —CH_Two-CH_Two-, -C
(R⁴²) = CH-, -N = N-, -CO-, -CO-
O-, -CO-CH_Two-O-, -CH_Two-CO-NH
-, -C (R ^{42 ''}) (R⁴³) -N (R^{44 ''})
-(Where R⁴², R^{42 ''}And R⁴³Is claim 1
Is synonymous with R^{44 ''}Is a hydrogen atom, C_1-6Al
Kill group or C_2-7It is an alkoxycarbonyl group)
Is -C (U) -N (R^{44 '' '})-(Where U is =
O or = S, R^{44 '''}Is R^{44 ''}Synonymous with
Yes) Yes; R^{38 ''}Has a hydrogen atom or a substituent
An optionally substituted aryl group; R^{39 ''}And R
^{40 ''}Are the same or different and are a hydrogen atom, C_1-6A
Rukiru group or C_2-7Is an alkoxycarbonyl group
Or R^{39 ''}And R^{40 ''}Adjacent to carbon
Being with a child, [Chemical 15] W ″ may be —CO— or —CH._Two-In
Yes; V₁And V_TwoIs as defined in claim 1; V_ThreeIs
-CH (R^{46 ''})-Or -N (R^{46 '''}) −
(Where R^{46 ' '}And R^{46 '''}Are the same or different
And is an aryl which may have a hydrogen atom or a substituent.
Is a radical group) may be formed]]
The indole compound according to claim 1, which is pharmaceutically acceptable
Salt or prodrug. 4. The indole compound according to claim ¹ , wherein R ¹ , R ² , R ⁴ , R ⁵ and R ⁶ are hydrogen atoms, or a pharmaceutically acceptable salt or prodrug thereof. 5. The indole compound according to claim 4, wherein R ³ is a halogen atom or a C _1-6 alkyl group, or a pharmaceutically acceptable salt or prodrug thereof. 6. X is ═O, A is a single bond, and B is The indole compound according to claim 5, which is: or a pharmaceutically acceptable salt or prodrug thereof. 7. X is ═NH, A is a single bond,
And B is [Chemical 17] The indole compound according to claim 4, which is: or a pharmaceutically acceptable salt or prodrug thereof. 8. R ⁶ and R ⁷ together with the adjacent nitrogen atom have the formula: The indole compound according to claims 1 to 3, which forms a pharmaceutically acceptable salt or prodrug thereof. 9. Benzoic acid 2- (5-chloro-1H-i)
Ndol-2-carbonyl) hydrazide, 2-amino ammonium
Benzoic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 2-hydroxybenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 3- (2- (2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazinocarbonyl) fe
Nylcarbamoyloxy) -2,2-dimethylpropio
Acid, benzoic acid 2- (5-chloro-1H-indole
-2-Carbonyl) -1-methylhydrazide, benzoic acid
2- (1-acetyl-5-chloro-1H-indole
-2-carbonyl) hydrazide, 5-chloro-1H-i
Ndol-2-carboxylic acid 2- (imino-phenyl-)
Methyl) hydrazide, 5-aminothiazole-4-cal
Boronic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, benzoic acid 2- (5-fluoro)
-1H-indole-2-carbonyl) hydrazide, shi
Chlorohexanecarboxylic acid 2- (5-fluoro-1H-
Indole-2-carbonyl) hydrazide, thiophene
-2-carboxylic acid 2- (5-fluoro-1H-indo)
2-carbonyl) hydrazide, 4-nitrobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 2-methylbenzoic acid 2- (5-ku)
Lolo-1H-indole-2-carbonyl) hydrazide
De, 4-methylbenzoic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, 2-methoxy
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 3-methoxybenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 4-methoxybenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 3-
Methylbenzoic acid 2- (5-chloro-1H-indole
-2-Carbonyl) hydrazide, 2-chlorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
) Hydrazide, 3-chlorobenzoic acid 2- (5-chloro)
-1H-indole-2-carbonyl) hydrazide,
4-chlorobenzoic acid 2- (5-chloro-1H-indo
2-carbonyl) hydrazide, 4- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) benzoic acid methyl ester, cyclohexa
Carboxylic acid 2- (5-chloro-1H-indole-
2-Carbonyl) hydrazide, 2,4-dichlorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nil) hydrazide, 2,6-dichlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2,4-difluorobenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
De, biphenyl-2-carboxylic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 3-
Fluorobenzoic acid 2- (5-chloro-1H-indole
-2-carbonyl) hydrazide, 4-fluorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 3-trifluoromethylbenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 4-trifluoromethylbenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-trifluoromethylbenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, benzoic acid 2- (5-methyl-1H-indo)
2-carbonyl) hydrazide, benzoic acid 2-
(5-chloro-3-methyl-1H-indole-2-ca
Lubonyl) hydrazide, benzoic acid 2- (5,7-dicu
Lolo-1H-indole-2-carbonyl) hydrazide
2-aminobenzoic acid 2- (5-isopropyl-1)
H-indole-2-carbonyl) hydrazide, 2-a
Mino-4-fluorobenzoic acid 2- (5-isopropyl)
-1H-indole-2-carbonyl) hydrazide, 2
-Aminobenzoic acid 2- (5-fluoro-1H-indo)
2-carbonyl) hydrazide, 2-aminobenzoic acid
Acid 2- (6-chloro-1H-indole-2-carb
Nyl) hydrazide, 3-amino-4- (2- (5-chloro)
B-1H-indole-2-carbonyl) hydrazinoca
Lubonyl) benzoic acid methyl ester, 3-aminoisononi
Cotinic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, isonicotinic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
De, nicotinic acid 2- (5-chloro-1H-indole
-2-carbonyl) hydrazide, pyridine-2-carbo
Acid 2- (5-chloro-1H-indole-2-cal
Bonyl) hydrazide, 3- (dimethylamino) benzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, N- (3- (2- (5-chloro-1H
-Indole-2-carbonyl) hydrazinocarboni
L) phenyl) acetamide, N- (2- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
Nocarbonyl) phenyl) acetamide, 4-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) -2-methylhydrazide, 2- (2- (2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazinocarbonyl) phenoxy) acetic acid methyl ester
2-, 2- (2- (2- (5-chloro-1H-indole
L-2-carbonyl) hydrazinocarbonyl) phenoki
Si) acetic acid, 2- (dimethylamino) benzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazide, 2- (2- (5-chloro-1H-indole
-2-Carbonyl) hydrazinocarbonyl) phenoxy
-N, N-dimethylacetamide, 2-methylamino ammonium
Benzoic acid 2- (5-chloro-1H-indole-2-ca)
Lubonyl) hydrazide, 2-amino-4-chlorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 2-amino-6-chlorobenzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2-amino-3-chlorobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-amino-5-chlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 4-cyanobenzoic acid 2- (5-chloro-1)
H-indole-2-carbonyl) hydrazide, 4-
(1H-tetrazol-5-yl) benzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydra
Zido, 3- (1H-tetrazol-5-yl) benzoic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 2- (2- (2- (5-chloro-1H
-Indole-2-carbonyl) hydrazinocarboni
Le) anilino) acetic acid, 2-aminobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide
2-amino-4-fluorobenzoic acid 2- (5-me
Chill-1H-indole-2-carbonyl) hydrazide
Demethyl, 2- (2- (5-methyl-1H-indole)
L-2-carbonyl) hydrazinocarbonyl) pheny
Carbamate, 2- (2- (5-chloro-1H-i)
Ndol-2-carbonyl) hydrazinocarbonyl)
Phenyl dimethyl carbamate, 2-aminobenzoic acid
2- (5-ethyl-1H-indole-2-carboni
Le) hydrazide, 2-amino-4,5-difluorobenzoate
Aromatic acid 2- (5-methyl-1H-indole-2-cal
Bonyl) hydrazide, 2- (2-hydroxyethoxy)
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 2- (3- (2- (5-chloro
B-1H-indole-2-carbonyl) hydrazinoca
Lubonyl) phenoxy) acetic acid methyl ester, 2- (3
-(2- (5-chloro-1H-indole-2-carb
Nil) hydrazinocarbonyl) phenoxy) acetic acid, 2-
(3- (2- (5-chloro-1H-indole-2-car
Rubonyl) hydrazinocarbonyl) phenoxy) -N,
N-dimethylacetamide, N- (1,2,3,4-then
Trahydro-7-nitro-2,4-dioxoquinazoline
-3-yl) -5-chloro-1H-indole-2-ca
Rubonamide, 2-methylthiazole-4-carboxylic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, 4- (2H- [1,2,4] triazo
3-l) benzoic acid 2- (5-chloro-1H-)
Indole-2-carbonyl) hydrazide, 3- (2H
-[1,2,4] Triazol-3-yl) benzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 1,3-dihydroxy-2-propyl
(2- (2- (5-chloro-1H-indole-2-car
Rubonyl) hydrazinocarbonyl) phenyl) carbame
, 3-((2- (2- (5-chloro-1H-indo
2-carbonyl) hydrazinocarbonyl) pheny
) Carbamoyloxy) -2,2-dimethylpropio
Acid, thiophene-2-carboxylic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide, fu
Lan-2-carboxylic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide, 2,6-dichloro
Ronicotinic acid 2- (5-chloro-1H-indole-
2-Carbonyl) hydrazide, 1H-pyrrole-2-ca
Rubonic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 1H-imidazole-4-ca
Rubonic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, pyrazine-2-carboxylic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, thiophene-3-carboxylic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, furan-3-carboxylic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide, 5
-Chlorothiophene-2-carboxylic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
3-chlorothiophene-2-carboxylic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
1-methyl-1H-pyrrole-2-carboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 5-methylthiophene-2-carboxylic acid
2- (5-chloro-1H-indole-2-carboni
Le) hydrazide, 3-methylthiophene-2-carvone
Acid 2- (5-chloro-1H-indole-2-carb
Nil) hydrazide, 2,6-difluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hi
Dolazide, 2,3-difluorobenzoic acid 2- (5-qua
Lolo-1H-indole-2-carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2- (naphthalene-1-carbonyl) hydrazide, 3,
4,5-Trifluorobenzoic acid 2- (5-chloro-1
H-indole-2-carbonyl) hydrazide, 2,
3,4,5-Tetrafluorobenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide,
2-Amino-4-methylbenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 2-
Amino-4-fluorobenzoic acid 2- (5-chloro-1
H-indole-2-carbonyl) hydrazide, 2-a
Mino-5-methylbenzoic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide, 2-amino
-6-Methylbenzoic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide, 2-amino-3
-Methylbenzoic acid 2- (5-chloro-1H-indole
2-L-carbonyl) hydrazide, 2-amino-4,5
-Difluorobenzoic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide, 3-aminothio
Phen-2-carboxylic acid 2- (5-chloro-1H-i
Ndol-2-carbonyl) hydrazide, 2-amino ammonium
Benzoic acid 2- (5-bromo-1H-indole-2-ca)
Lubonyl) hydrazide, 2-amino-4-fluorobenzoate
Aromatic acid 2- (5-bromo-1H-indole-2-cal
Bonyl) hydrazide, 1H-pyrazole-4-carvone
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide, methyl (2- (2- (5-fluor
B-1H-indole-2-carbonyl) hydrazinoca
Rubonyl) phenyl) carbamate, 1-methyl-1H
-Pyrrole-2-carboxylic acid 2- (5-methyl-1H)
-Indole-2-carbonyl) hydrazide, thiophe
-3-carboxylic acid 2- (5-methyl-1H-indo)
2-carbonyl) hydrazide, 4H-thieno
[3,2-b] Pyrrole-5-carboxylic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
De, phenyl (2- (2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazinocarbonyl) fe
Nyl) carbamate, benzyl (2- (2- (5-
Lolo-1H-indole-2-carbonyl) hydrazino
Carbonyl) phenyl) carbamate, 2-hydroxy
Ethyl (2- (2- (5-chloro-1H-indole
-2-carbonyl) hydrazinocarbonyl) phenyl)
Carbamate, 3-hydroxypropyl (2- (2-
(5-chloro-1H-indole-2-carbonyl) hi
Dorazinocarbonyl) phenyl) carbamate, 2-
((2- (5-chloro-1H-indole-2-carb
Nyl) hydrazinocarbonyl) phenyl) carbamoyl
Oxy) acetic acid, 2-((2- (2- (5-chloro-1H
-Indole-2-carbonyl) hydrazinocarboni
) Phenyl) carbamoyloxymethyl) -2-methyl
Lumalonic acid, methyl 2- (2- (5-chloro-1H-
Indole-2-carbonyl) hydrazinocarbonyl)
Phenyl carbamate, cyclohexanecarboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
-1-Methylhydrazide, thiophene-2-carboxylic acid
2- (5-chloro-1H-indole-2-carboni
) -1-methyl hydrazide, benzoic acid 2- (1H-
Indole-2-carbonyl) hydrazide, benzoic acid
2- (5-chloro-1-methyl-1H-indole-2
-Carbonyl) hydrazide, benzoic acid 2- (5-meth)
Xy-1H-indole-2-carbonyl) hydrazide
De, benzoic acid 2- (5-isopropyl-1H-india
2-carbonyl) hydrazide, benzoic acid 2-
(5-nitro-1H-indole-2-carbonyl) hi
Dorazide, benzoic acid 2- (5-benzyloxy-1H
-Indole-2-carbonyl) hydrazide, benzoic acid
2- (6-chloro-1H-indole-2-carboni
Le) hydrazide, 6H-thieno [2,3-b] pyrrole
-5-carboxylic acid 2- (5-chloro-1H-indole
2-L-carbonyl) hydrazide, 5-chloro-1H-
Indole-2-carboxylic acid 2-((2-Fluorov
Phenyl) -imino-methyl) hydrazide, 5-chloro-
1 H-indole-2-carboxylic acid 2-((3-flo
Orophenyl) -imino-methyl) hydrazide, 5-qua
Lolo-1H-indole-2-carboxylic acid 2-((4
-Fluorophenyl) -imino-methyl) hydrazide,
5-chloro-1H-indole-2-carboxylic acid 2-
(Imino- (p-tolyl) -methyl) hydrazide, 5-
Chloro-1H-indole-2-carboxylic acid 2-
((4-chlorophenyl) -imino-methyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((3-chlorophenyl) -imino-methyl) hydr
Lazide, 5-chloro-1H-indole-2-carvone
Acid 2-((2-chlorophenyl) -imino-methyl)
Hydrazide, 5-chloro-1H-indole-2-cal
Boronic acid 2- (imino- (o-tolyl) -methyl) hydr
Lazide, 5-chloro-1H-indole-2-carvone
Acid 2- (imino- (m-tolyl) -methyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (thiophen-2-yl) -methyl) hi
Dorazide, 5-chloro-1H-indole-2-carb
Acid 2- (imino- (pyridin-2-yl) -methyl ester
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2-((furan-2-yl) -imino-me
Chill) hydrazide, 5-chloro-1H-indole-2
-Carboxylic acid 2-((2-chloro-6-fluorophe
Nyl) -imino-methyl) hydrazide, 5-chloro-1
H-indole-2-carboxylic acid 2- (imino- (2
-Trifluoromethylphenyl) -methyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (pyrazin-2-yl) -methyl) hydr
Lazide, 3-aminobenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 3-meth
Xybenzoic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 5-amino-2-methyl
Thiazole-4-carboxylic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 5-chloro
B-1H-indole-2-carboxylic acid (1,2,
3,4-tetrahydro-2,4-dioxoquinazoline-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid (2,3-dihydro-2,4-dioxo
-4H-benzo [e] [1,3] oxazin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boronic acid (1,2,3,4-tetrahydro-4-oxo
-2-thioxoquinazolin-3-yl) amide, 5-qua
Lolo-1H-indole-2-carboxylic acid (3,4-
Dihydro-2-methyl-4-oxoquinazolin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (3,4-dihydro-4-oxoquinazoline-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid (1,2,3,4-tetrahydro-4-
Oxoquinazolin-3-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid (1,2,3,4-
Tetrahydro-2,5-dioxo-5H-benzo [e]
[1,4] diazepin-4-yl) amide, 5-chloro
-1H-indole-2-carboxylic acid (2,3,4,
5-Tetrahydro-3,5-dioxo-benzo [f]
[1,4] Oxazepin-4-yl) amide, 5-i
Sopropyl-1H-indole-2-carboxylic acid
(1,2,3,4-tetrahydro-2,4-dioxoki
Nazolin-3-yl) amide, 5-isopropyl-1H
-Indole-2-carboxylic acid (7-fluoro-1,
2,3,4-tetrahydro-2,4-dioxoquinazoli
N-3-yl) amide, 5-fluoro-1H-indole
Le-2-carboxylic acid (1,2,3,4-tetrahydro
-2,4-dioxoquinazolin-3-yl) amide, 6
-Chloro-1H-indole-2-carboxylic acid (1,
2,3,4-tetrahydro-2,4-dioxoquinazoli
N-3-yl) amide, 3-((5-chloro-1H-i
Ndole-2-carbonyl) amino) -1,2,3,4
-Tetrahydro-2,4-dioxoquinazoline-7-ca
Rubonic acid methyl ester, 3-((5-chloro-1H-
Indole-2-carbonyl) amino) -1,2,3
4-Tetrahydro-2,4-dioxoquinazoline-7-
Carboxylic acid, 5-chloro-1H-indole-2-cal
Boronic acid (1,2,3,4-tetrahydro-2,4-di
Oxo-6- (trifluoroacetylamino) quinazoli
N-3-yl) amide, 5-chloro-1H-indole
-2-carboxylic acid (6-amino-1,2,3,4-tetracarboxylic acid
Trahydro-2,4-dioxoquinazolin-3-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (5-chloro-1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-3-yl) amide, 5-
Chloro-1H-indole-2-carboxylic acid (6-
Lolo-1,2,3,4-tetrahydro-2,4-dioki
Soquinazolin-3-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid (7-chloro-1,2,
3,4-tetrahydro-2,4-dioxoquinazoline-
3-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid (8-chloro-1,2,3,4-tetra
Hydro-2,4-dioxoquinazolin-3-yl) ami
2- (3-((5-chloro-1H-indole-2
-Carbonyl) amino) -1,2,3,4-tetrahydr
(2,4-dioxoquinazolin-1-yl) acetic acid, 2
-(3-((5-chloro-1H-indole-2-cal
Bonyl) amino) -1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-1-yl) acetic acid methyl ester
Stell, 5-methyl-1H-indole-2-carvone
Acid (1,2,3,4-tetrahydro-2,4-dioki
Soquinazolin-3-yl) amide, 5-methyl-1H-
Indole-2-carboxylic acid (7-fluoro-1,
2,3,4-tetrahydro-2,4-dioxoquinazoli
N-3-yl) amide, 5-ethyl-1H-indole
-2-carboxylic acid (1,2,3,4-tetrahydro-
2,4-dioxoquinazolin-3-yl) amide, 5-
Methyl-1H-indole-2-carboxylic acid (6,7
-Difluoro-1,2,3,4-tetrahydro-2,4
-Dioxoquinazolin-3-yl) amide, 5-methyl
-1H-indole-2-carboxylic acid (1,2,3,
4-tetrahydro-6-methoxy-2,4-dioxoki
Nazolin-3-yl) amide, 5-methyl-1H-yne
Dole-2-carboxylic acid (1,2,3,4-tetrahydo
Doro-6-hydroxy-2,4-dioxoquinazoline-
3-yl) amide, acetic acid 3-((5-methyl-1H-
Indole-2-carbonyl) amino) -1,2,3
4-Tetrahydro-2,4-dioxoquinazoline-6-
Ile ester, 5-chloro-1H-indole-2-ca
Rubonic acid (1,2,3,4-tetrahydro-2,4-
Dioxo-1-propylquinazolin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(1,2,3,4-tetrahydro-1-methyl-2,4
-Dioxoquinazolin-3-yl) amide, 5-chloro
-1H-indole-2-carboxylic acid (2,4-dio
Xoxoperhydropyrimidin-3-yl) amide, 5-qua
Lolo-1H-indole-2-carboxylic acid (4-Oki
So-2-thioxoperhydropyrimidin-3-yl) a
Mido, 5-chloro-1H-indole-2-carboxylic acid
(2,4-dioxo-1-phenylperhydropyrimy
Zin-3-yl) amide, 5-chloro-1H-indole
2-carboxylic acid (4-oxo-1-phenylper)
Hydropyrimidin-3-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid (1- (4-fluor
Rophenyl) -2,4-dioxoperhydropyrimidine
-3-yl) amide, 5-chloro-1H-indole-
2-carboxylic acid (2,4-dioxo-1- (pyridine
-2-yl) perhydropyrimidin-3-yl) ami
De, 5-chloro-1H-indole-2-carboxylic acid
(1- (3-fluorophenyl) -2,4-dioxopa
-Hydropyrimidin-3-yl) amide, 5-chloro-
1H-indole-2-carboxylic acid (1- (2-full
Orophenyl) -2,4-dioxoperhydropyrimidi
N-3-yl) amide, 5-fluoro-1H-indole
2-carboxylic acid (2,4-dioxo-1-phenyl
Lu-perhydropyrimidin-3-yl) amide, 5-me
Chill-1H-indole-2-carboxylic acid (2,4-
Dioxo-1-phenyl-perhydropyrimidine-3-
Yl) amide, 5-chloro-1H-indole-2-ca
Rubonic acid (1- (3-chlorophenyl) -2,4-di
Oxoperhydropyrimidin-3-yl) amide, 5-
Chloro-1H-indole-2-carboxylic acid (2,4
-Dioxo-1- (m-tolyl) perhydropyrimidine
-3-yl) amide, 5-chloro-1H-indole-
2-carboxylic acid (2,4-dioxo-1- (p-tri
Le) perhydropyrimidin-3-yl) amide, 5-
Lolo-1H-indole-2-carboxylic acid (1- (4
-Chlorophenyl) -2,4-dioxoperhydropyr
Midin-3-yl) amide, 5-chloro-1H-indo
2-carboxylic acid (2,4-dioxo-1- (o
-Tolyl) perhydropyrimidin-3-yl) amide,
5-chloro-1H-indole-2-carboxylic acid
((4S) -2,5-Dioxo-4-phenylimidazo
Lydin-1-yl) amide, 5-chloro-1H-indo
2-carboxylic acid (2,4-dioxo-1-phen
Nylimidazolidin-3-yl) amide, 5-chloro-
1H-indole-2-carboxylic acid (4-oxo-1
-Phenyl-2-thioxoimidazolidin-3-yl)
Amide, 5-chloro-1H-indole-2-carvone
Acid (4-oxo-1-phenylimidazolidine-3-
Yl) amide, 5-chloro-1H-indole-2-ca
Rubonic acid (2-oxo-1-phenylimidazolidine
-3-yl) amide, 5-chloro-1H-indole-
2-carboxylic acid ((4R) -2,5-dioxo-4-
Phenylimidazolidin-1-yl) amide, 5-chloro
B-1H-indole-2-carboxylic acid ((4S)-
1,3-Dioxo-perhydropyrrolo [1,2-c] ii
Midazol-2-yl) amide, 5-chloro-1H-i
Ndol-2-carboxylic acid ((4R) -1,3-dio
Xoxo-perhydropyrrolo [1,2-c] imidazole-
2-yl) amide, 5-chloro-1H-indole-2
-Carboxylic acid ((4S) -4-benzyl-2,5-di
Oxoimidazolidin-1-yl) amide, 5-chloro
-1H-indole-2-carboxylic acid ((4R) -4
-Benzyl-2,5-dioxoimidazolidin-1-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (2,4-dioxoimidazolidin-3-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (1-methyl-2,5-dioxo-4-phenyl
Ruimidazolidin-1-yl) amide, 5-chloro-1
H-indole-2-carboxylic acid (2,4-dioxo
-1- (4-fluorophenyl) imidazolidine-3-
Yl) amide, 5-chloro-1H-indole-2-ca
Rubonic acid (2,5-dioxo-4- (2-fluorophenyl)
Phenyl) imidazolidin-1-yl) amide, 5-chloro
B-1H-indole-2-carboxylic acid (2,5-di
Oxo-4- (2-thienyl) imidazolidin-1-i
) Amide, 5-chloro-1H-indole-2-cal
Boric acid (2,5-dioxo-4- (4-fluorophene)
Nyl) imidazolidin-1-yl) amide, 5-chloro
-1H-indole-2-carboxylic acid (2,5-dio
Xo-4- (4-chlorophenyl) imidazolidine-1
-Yl) amide, 5-chloro-1H-indole-2-
Carboxylic acid ((4S) -2,5-dioxo-4- (4
-Hydroxyphenyl) imidazolidin-1-yl) a
Mido, 5-chloro-1H-indole-2-carboxylic acid
((4S) -2,5-dioxo-4- (4-methoxy
Phenyl) imidazolidin-1-yl) amide, 5-chloro
Lolo-1H-indole-2-carboxylic acid ((4R)
-2,5-dioxo-4- (4-methoxyphenyl) ii
Midazolidin-1-yl) amide, 5-chloro-1H-
Indole-2-carboxylic acid 2- (anilinocarboni
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2- (phenylthiocarbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2- (2-phenylacetyl) hydrazide, 5-chloro
-1H-indole-2-carboxylic acid 2- (2-oxy
So-2-phenylacetyl) hydrazide, 5-chloro-
1H-indole-2-carboxylic acid 2-((2-full
Orophenyl) aminocarbonyl) hydrazide, 5-chloro
Lolo-1H-indole-2-carboxylic acid 2-((3
-Fluorophenyl) aminocarbonyl) hydrazide,
5-chloro-1H-indole-2-carboxylic acid 2-
((4-Fluorophenyl) aminocarbonyl) hydra
Zido, 5-chloro-1H-indole-2-carboxylic acid
2- (anilinocarbonyl) -2-methylhydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((2-chloroanilino) carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((3-chloroanilino) carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((4-chloroanilino) carbonyl) hydrazide
De, 5-chloro-1H-indole-2-carboxylic acid
2-((1-phenylcyclopropane) carbonyl) hi
Dorazide, 5-chloro-1H-indole-2-carb
2-((1-phenylcyclopentane) carbonic acid
Le) hydrazide, 5-chloro-1H-indole-2-
Carboxylic acid 2-((1-phenylcyclohexane) ca
Lubonyl) hydrazide, 5-chloro-1H-indole
-2-carboxylic acid 2- (2-phenylpropanoyl)
Hydrazide, 5-chloro-1H-indole-2-cal
Boronic acid 2- (3-hydroxy-2-phenylpropano)
Il) hydrazide, 5-chloro-1H-indole-2
-Carboxylic acid 2- (2-methyl-2-phenylpropa
Noyl) hydrazide, 5-chloro-1H-indole-
2-carboxylic acid 2-((2S) -2-amino-2-fur
Phenylacetyl) hydrazide, N- (2- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide
No) -2-oxo-1-phenylethyl) acetami
2-morpholinoethyl (2-((2- (5-chloro
B-1H-indole-2-carbonyl) hydrazino)
Carbonyl) phenyl) carbamate p-toluene
Ruphonate, 2-amino-4,5-difluorobenzoic acid
2- (5-methyl-1H-indole-2-carboni
Le) hydrazide benzene sulfonate, 2-amino-
4-Fluorobenzoic acid 2- (5-chloro-1H-yne
Dole-2-carbonyl) hydrazide benzenesulfo
Phosphate, 3-dimethylaminobenzoic acid 2- (5-chloro
B-1H-indole-2-carbonyl) hydrazide
Methanesulfonate, 2-amino-4-fluorobenzoic acid
Acid 2- (5-chloro-1H-indole-2-carb
Nyl) hydrazide hydrochloride, 2-amino-4-fluoro
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide p-toluenesulfonate,
2-Amino-4-fluorobenzoic acid 2- (5-chloro
-1H-indole-2-carbonyl) hydrazide p
-Toluene sulfonate, 2-amino-4-fluoro ammonium
Benzoic acid 2- (5-chloro-1H-indole-2-ca)
Rubonyl) hydrazide p-toluenesulfonate, 2
-Amino-4-fluorobenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide p-
Toluenesulfonate, 2-aminobenzoic acid 2- (5
-Methyl-1H-indole-2-carbonyl) hydra
Zido p-toluenesulfonate, 2-aminobenzoic acid
2- (5-methyl-1H-indole-2-carboni
Le) hydrazide benzene sulfonate, 2-amino-
4-Fluorobenzoic acid 2- (5-methyl-1H-yne
Dole-2-carbonyl) hydrazide benzenesulfo
Phosphate, 2-aminobenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide p-tolu
Ensulfonate, 5-chloro-1H-indole-2
-Carboxylic acid 2-((2-chlorophenyl) -imino
-Methyl) hydrazide methanesulfonate, 5-chloro
B-1H-indole-2-carboxylic acid 2-((2-
Chlorophenyl) -imino-methyl) hydrazide p-
Toluene sulfonate, 5-chloro-1H-indole
-2-carboxylic acid 2-((2-chlorophenyl) -i
Mino-methyl) hydrazide hydrochloride, 5-chloro-1H
-Indole-2-carboxylic acid 2- (imino-phenyl
L-methyl) hydrazide methanesulfonate, 5-chloro
Lolo-1H-indole-2-carboxylic acid 2-((2
-Chlorophenyl) -imino-methyl) hydrazide
Tendioate, 5-chloro-1H-indole-2-cal
Boronic acid 2-((2-fluorophenyl) -imino-me
Chill) hydrazide hydrochloride, 5-chloro-1H-indo
2-carboxylic acid 2-((2-fluorophenyl
) -Imino-methyl) hydrazide methanesulfonic acid
Salt, 5-chloro-1H-indole-2-carboxylic acid
2-((1-imino-2-phenylethyl) hydrazide
Methanesulfonate, 5-chloro-1H-indole
-2-carboxylic acid 2-((3-fluorophenyl)-
Imino-methyl) hydrazide hydrochloride, 5-chloro-1
H-indole-2-carboxylic acid 2-((3,4-di
Fluorophenyl) -imino-methyl) hydrazide
Tansulphonate, 5-chloro-1H-indole-2
-Carboxylic acid 2- (imino- (2-methoxyphenyl
) -Methyl) hydrazide methanesulfonate, 5-
Chloro-1H-indole-2-carboxylic acid 2-
((2,6-difluorophenyl) -imino-methyl)
Hydrazide methanesulfonate, 5-chloro-1H-
Indole-2-carboxylic acid 2-((2,4-diflu
Orophenyl) -imino-methyl) hydrazide methane
Sulfonate, 5-chloro-1H-indole-2-ca
Rubonic acid 2-((1,2-dimethyl-1H-pyrrole
-5-yl) -imino-methyl) hydrazide methan
Ruphonate, 2-aminobenzoic acid 2- (5-methyl-)
1H-indole-2-carbonyl) hydrazide p-
Toluenesulfonate, 2-aminobenzoic acid 2- (5
-Methyl-1H-indole-2-carbonyl) hydra
Zido benzene sulfonate, and 2-amino-4-
Fluorobenzoic acid 2- (5-methyl-1H-indole
Lu-2-carbonyl) hydrazide benzenesulfonic acid
The indole according to claim 1, which is selected from the group consisting of salts.
Compound, a pharmaceutically acceptable salt or prodrug thereof. 10. Benzoic acid 2- (5-chloro-1H-)
Indole-2-carbonyl) hydrazide, 2-aminobenzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 2-hydroxybenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 3- (2- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenylcarbamoyloxy) -2,2-dimethylpropionic acid, benzoic acid 2- (5-chloro-1H -Indole-2-carbonyl) -1-methylhydrazide, benzoic acid 2- (1-acetyl-5-chloro-1H-indole-2-carbonyl) hydrazide, 5-chloro-1H-
Indole-2-carboxylic acid 2- (imino-phenyl-methyl) hydrazide, 5-aminothiazole-4-carboxylic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, benzoic acid 2- (5-fluoro-1H-indole-2-carbonyl) hydrazide,
Cyclohexanecarboxylic acid 2- (5-fluoro-1H
-Indole-2-carbonyl) hydrazide, thiophene-2-carboxylic acid 2- (5-fluoro-1H-indole-2-carbonyl) hydrazide, 4-nitrobenzoic acid 2- (5-chloro-1H-indole-2- Carbonyl) hydrazide, 2-methylbenzoic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide, 4-methylbenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-methoxybenzoic acid 2- (5-chloro-1H-indole- 2-
Carbonyl) hydrazide, 3-methoxybenzoic acid 2-
(5-Chloro-1H-indole-2-carbonyl) hydrazide, 4-methoxybenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 3-
Methylbenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-chlorobenzoic acid
2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 3-chlorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide,
4-Chlorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 4- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) benzoic acid methyl ester, cyclohexanecarboxylic acid 2- (5-chloro-1H-indole-
2-carbonyl) hydrazide, 2,4-dichlorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2,6-dichlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hydrazide, 2,4-difluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, biphenyl-2-carboxylic acid 2- (5- Chloro-
1H-indole-2-carbonyl) hydrazide, 3-
Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 3-trifluoromethylbenzoic acid
2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 4-trifluoromethylbenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-trifluoromethylbenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hydrazide, benzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide, benzoic acid 2-
(5-chloro-3-methyl-1H-indole-2-carbonyl) hydrazide, benzoic acid 2- (5,7-dichloro-1H-indole-2-carbonyl) hydrazide, 2-aminobenzoic acid 2- (5- Isopropyl-1
H-indole-2-carbonyl) hydrazide, 2-amino-4-fluorobenzoic acid 2- (5-isopropyl-1H-indole-2-carbonyl) hydrazide, 2
-Aminobenzoic acid 2- (5-fluoro-1H-indole-2-carbonyl) hydrazide, 2-aminobenzoic acid 2- (6-chloro-1H-indole-2-carbonyl) hydrazide, 3-amino-4- ( 2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) benzoic acid methyl ester, 3-aminoisonicotinic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, isonicotinic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide, nicotinic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, pyridine-2-carboxylic acid 2- (5-chloro-1H-indole-2- Carbonyl) hydrazide, 3- (dimethylamino) benzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, N- (3- (2- (5-chloro-1H)
-Indole-2-carbonyl) hydrazinocarbonyl) phenyl) acetamide, N- (2- (2- (5-
Chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl) acetamide, 4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) -2-methylhydrazide, 2- (2- (2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazinocarbonyl) phenoxy) acetic acid methyl ester, 2- (2- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenoxy) acetic acid, 2- (dimethylamino) benzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hydrazide, 2- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenoxy-N, N-dimethylacetamide, 2-methylamino Benzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-amino-4-chlorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-amino-6 -Chlorobenzoic acid
2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-amino-3-chlorobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 2-amino-5-chlorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hydrazide, 4-cyanobenzoic acid 2- (5-chloro-1
H-indole-2-carbonyl) hydrazide, 4-
(1H-tetrazol-5-yl) benzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydrazide, 3- (1H-tetrazol-5-yl) benzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2- (2- (2 -(5-chloro-1H
-Indole-2-carbonyl) hydrazinocarbonyl) anilino) acetic acid, 2-aminobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide, 2-amino-4-fluorobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide, methyl 2- (2- (5-methyl-1H) -Indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamate, 2- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl dimethylcarbamate, 2-aminobenzoic acid
2- (5-Ethyl-1H-indole-2-carbonyl) hydrazide, 2-amino-4,5-difluorobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide, 2- (2- Hydroxyethoxy)
Benzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 2- (3- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenoxy) acetic acid methyl ester, 2- (3
-(2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenoxy) acetic acid, 2-
(3- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenoxy) -N,
N-dimethylacetamide, N- (1,2,3,4-tetrahydro-7-nitro-2,4-dioxoquinazolin-3-yl) -5-chloro-1H-indole-2-carboxylic acid amide, 2 -Methylthiazol-4-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 4- (2H- [1,2,4] triazol-3-yl) benzoic acid 2- (5- Chloro-1H-
Indole-2-carbonyl) hydrazide, 3- (2H
-[1,2,4] Triazol-3-yl) benzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 1,3-dihydroxy-2-propyl
(2- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamate, 3-((2- (2- (5-chloro-1H-indole-2-carbonyl) hydra) Dinocarbonyl) phenyl) carbamoyloxy) -2,2-dimethylpropionic acid, thiophene-2-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, furan-2-carboxylic acid 2- (5 -Chloro-1H-indole-2-carbonyl) hydrazide, 2,6-dichloronicotinic acid 2- (5-chloro-1H-indole-
2-Carbonyl) hydrazide, 1H-pyrrole-2-carboxylic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, 1H-imidazole-4-carboxylic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide, pyrazine-2-carboxylic acid
2- (5-chloro-1H-indole-2-carbonyl) hydrazide, thiophen-3-carboxylic acid 2-
(5-chloro-1H-indole-2-carbonyl) hydrazide, furan-3-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 5
-Chlorothiophene-2-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide,
3-Chlorothiophene-2-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 1-methyl-1H-pyrrole-2-carboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide, 5-methylthiophene-2-carboxylic acid
2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 3-methylthiophene-2-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2,6-difluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hydrazide, 2,3-difluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid
2- (naphthalene-1-carbonyl) hydrazide, 3,
4,5-Trifluorobenzoic acid 2- (5-chloro-1
H-indole-2-carbonyl) hydrazide, 2,
3,4,5-tetrafluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide,
2-Amino-4-methylbenzoic acid 2- (5-chloro-
1H-indole-2-carbonyl) hydrazide, 2-
Amino-4-fluorobenzoic acid 2- (5-chloro-1
H-indole-2-carbonyl) hydrazide, 2-amino-5-methylbenzoic acid 2- (5-chloro-1H-
Indole-2-carbonyl) hydrazide, 2-amino-6-methylbenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-amino-3
-Methylbenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-amino-4,5
-Difluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 3-aminothiophene-2-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, 2-amino Benzoic acid 2- (5-bromo-1H-indole-2-carbonyl) hydrazide, 2-amino-4-fluorobenzoic acid 2- (5-bromo-1H-indole-2-carbonyl) hydrazide, 1H-pyrazole-4 -Carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide, methyl (2- (2- (5-fluoro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamate, 1- Methyl-1H
-Pyrrole-2-carboxylic acid 2- (5-methyl-1H)
-Indole-2-carbonyl) hydrazide, thiophen-3-carboxylic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide, 4H-thieno [3,2-b] pyrrole-5-carboxylic acid 2- (5-
Chloro-1H-indole-2-carbonyl) hydrazide, phenyl (2- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamate, benzyl (2- (2- (5- Chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamate, 2-hydroxyethyl (2- (2- (5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl)
Carbamate, 3-hydroxypropyl (2- (2-
(5-chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamate, 2-
((2- (5-Chloro-1H-indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamoyloxy) acetic acid, 2-((2- (2- (5-chloro-1H
-Indole-2-carbonyl) hydrazinocarbonyl) phenyl) carbamoyloxymethyl) -2-methylmalonic acid, methyl 2- (2- (5-chloro-1H-
Indole-2-carbonyl) hydrazinocarbonyl)
Phenyl carbamate, cyclohexanecarboxylic acid 2
-(5-chloro-1H-indole-2-carbonyl)
-1-Methylhydrazide, thiophene-2-carboxylic acid 2- (5-chloro-1H-indole-2-carbonyl) -1-methylhydrazide, benzoic acid 2- (1H-
Indole-2-carbonyl) hydrazide, benzoic acid
2- (5-chloro-1-methyl-1H-indole-2
-Carbonyl) hydrazide, benzoic acid 2- (5-methoxy-1H-indole-2-carbonyl) hydrazide, benzoic acid 2- (5-isopropyl-1H-indole-2-carbonyl) hydrazide, benzoic acid 2-
(5-Nitro-1H-indole-2-carbonyl) hydrazide, benzoic acid 2- (5-benzyloxy-1H
-Indole-2-carbonyl) hydrazide, benzoic acid 2- (6-chloro-1H-indole-2-carbonyl) hydrazide, 6H-thieno [2,3-b] pyrrole-5-carboxylic acid 2- (5-chloro) -1H-indole-2-carbonyl) hydrazide, 5-chloro-1H-
Indole-2-carboxylic acid 2-((2-fluorophenyl) -imino-methyl) hydrazide, 5-chloro-
1H-indole-2-carboxylic acid 2-((3-fluorophenyl) -imino-methyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid 2-((4
-Fluorophenyl) -imino-methyl) hydrazide,
5-chloro-1H-indole-2-carboxylic acid 2-
(Imino- (p-tolyl) -methyl) hydrazide, 5-
Chloro-1H-indole-2-carboxylic acid 2-
((4-chlorophenyl) -imino-methyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid
2-((3-chlorophenyl) -imino-methyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid 2-((2-chlorophenyl) -imino-methyl)
Hydrazide, 5-chloro-1H-indole-2-carboxylic acid 2- (imino- (o-tolyl) -methyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid 2- (imino- (m-tolyl ) -Methyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (thiophen-2-yl) -methyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid 2- (imino- (pyridin-2-yl) -methyl) hydrazide, 5-chloro- 1H-Indole-2-
Carboxylic acid 2-((furan-2-yl) -imino-methyl) hydrazide, 5-chloro-1H-indole-2
-Carboxylic acid 2-((2-chloro-6-fluorophenyl) -imino-methyl) hydrazide, 5-chloro-1
H-indole-2-carboxylic acid 2- (imino- (2
-Trifluoromethylphenyl) -methyl) hydrazide, 5-chloro-1H-indole-2-carboxylic acid
2- (imino- (pyrazin-2-yl) -methyl) hydrazide, 3-aminobenzoic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 3-methoxybenzoic acid 2- (5-chloro-1H-indole-
2-Carbonyl) hydrazide, 5-amino-2-methylthiazole-4-carboxylic acid 2- (5-chloro-1H
-Indole-2-carbonyl) hydrazide, 2-morpholinoethyl (2-((2- (5-chloro-1H-indole-2-carbonyl) hydrazino) carbonyl)
Phenyl) carbamate p-toluenesulfonate,
2-Amino-4,5-difluorobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide benzenesulfonate, 2-amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-
Carbonyl) hydrazide benzene sulfonate, 3-
Dimethylaminobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide methanesulfonate, 2-amino-4-fluorobenzoic acid 2- (5
-Chloro-1H-indole-2-carbonyl) hydrazide hydrochloride, 2-amino-4-fluorobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide p-toluenesulfonate, 2-amino-
4-Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-amino-4-fluorobenzoic acid 2-
(5-Chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-amino-4
-Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-aminobenzoic acid 2- (5-methyl-1)
H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-aminobenzoic acid 2- (5-
Methyl-1H-indole-2-carbonyl) hydrazide benzenesulfonate, 2-amino-4-fluorobenzoic acid 2- (5-methyl-1H-indole-2-
Carbonyl) hydrazide benzene sulfonate, 2-
Aminobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((2-chlorophenyl) -imino-methyl ) Hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((2-chlorophenyl) -imino-methyl) hydrazide p-toluenesulfonate, 5-chloro-1H-indole-2- Carboxylic acid 2-((2-chlorophenyl) -imino-methyl) hydrazide hydrochloride, 5-chloro-1H-indole-2-carboxylic acid 2- (imino-phenyl-methyl) hydrazide methanesulfonate, 5-chloro- 1
H-indole-2-carboxylic acid 2-((2-chlorophenyl) -imino-methyl) hydrazide butene diacid salt, 5-chloro-1H-indole-2-carboxylic acid
2-((2-fluorophenyl) -imino-methyl) hydrazide hydrochloride, 5-chloro-1H-indole-2
-Carboxylic acid 2-((2-fluorophenyl) -imino-methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((1
-Imino-2-phenylethyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((3-fluorophenyl) -imino-methyl) hydrazide hydrochloride, 5-chloro-1H- Indole-2-carboxylic acid 2-((3,4-difluorophenyl) -imino-methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2- (imino- (2-methoxyphenyl) ) -Methyl) hydrazide methanesulfonate, 5-chloro-1
H-indole-2-carboxylic acid 2-((2,6-difluorophenyl) -imino-methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2
-Carboxylic acid 2-((2,4-difluorophenyl)
-Imino-methyl) hydrazide methanesulfonate,
5-chloro-1H-indole-2-carboxylic acid 2-
((1,2-Dimethyl-1H-pyrrol-5-yl)-
Imino-methyl) hydrazide methanesulfonate, 2
-Aminobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-aminobenzoic acid 2- (5-methyl-1H)
-Indole-2-carbonyl) hydrazide benzenesulfonate and 2-amino-4-fluorobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide benzenesulfonate. The indole compound according to claim 1, a pharmaceutically acceptable salt or prodrug thereof. 11. 2-Morpholinoethyl (2-((2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazino) carbonyl) phenyl) carbamate p
-Toluenesulfonate, 2-amino-4,5-difluorobenzoic acid 2- (5-methyl-1H-indole-
2-carbonyl) hydrazide benzene sulfonate,
2-Amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide benzenesulfonate, 3-dimethylaminobenzoic acid 2
-(5-chloro-1H-indole-2-carbonyl)
Hydrazide methanesulfonate, 2-amino-4-fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide hydrochloride, 2-amino-
4-Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-amino-4-fluorobenzoic acid 2-
(5-Chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-amino-4
-Fluorobenzoic acid 2- (5-chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-amino-4-fluorobenzoic acid 2-
(5-chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-aminobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2 −
Aminobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide benzene sulfonate, 2-amino-4-fluorobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide benzene Sulfonate, 2-aminobenzoic acid 2-
(5-Chloro-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 5-chloro-1
H-indole-2-carboxylic acid 2-((2-chlorophenyl) -imino-methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((2-chlorophenyl) -imino- Methyl) hydrazide p-toluenesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((2-
Chlorophenyl) -imino-methyl) hydrazide hydrochloride, 5-chloro-1H-indole-2-carboxylic acid
2- (imino-phenyl-methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((2-chlorophenyl) -imino-methyl) hydrazide butene diacid salt, 5-chloro- 1H-
Indole-2-carboxylic acid 2-((2-fluorophenyl) -imino-methyl) hydrazide hydrochloride, 5-
Chloro-1H-indole-2-carboxylic acid 2-
((2-Fluorophenyl) -imino-methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2-((1-imino-2-phenylethyl) hydrazide methanesulfonate, 5 -Chloro-1H-indole-2-carboxylic acid 2-((3
-Fluorophenyl) -imino-methyl) hydrazide
Hydrochloride, 5-chloro-1H-indole-2-carboxylic acid 2-((3,4-difluorophenyl) -imino-
Methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-carboxylic acid 2- (imino-)
(2-Methoxyphenyl) -methyl) hydrazide methanesulfonate, 5-chloro-1H-indole-2-
Carboxylic acid 2-((2,6-difluorophenyl)-
Imino-methyl) hydrazide methanesulfonate, 5
-Chloro-1H-indole-2-carboxylic acid 2-
((2,4-difluorophenyl) -imino-methyl)
Hydrazide methanesulfonate, 5-chloro-1H-
Indole-2-carboxylic acid 2-((1,2-dimethyl-1H-pyrrol-5-yl) -imino-methyl) hydrazide methanesulfonate, 2-aminobenzoic acid
2- (5-Methyl-1H-indole-2-carbonyl) hydrazide p-toluenesulfonate, 2-aminobenzoic acid 2- (5-methyl-1H-indole-2
-Carbonyl) hydrazide benzene sulphonate and 2-amino-4-fluorobenzoic acid 2- (5-methyl-1H-indole-2-carbonyl) hydrazide benzene sulphonate. Indole compounds, their pharmaceutically acceptable salts or prodrugs. 12. A pharmaceutical composition comprising the indole compound according to any one of claims 1 to 11, a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier. 13. An HL comprising the indole compound according to any one of claims 1 to 11, a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier.
GPa inhibitor. 14. A therapeutic agent for diabetes comprising the indole compound according to any one of claims 1 to 11, a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier. 15. The pharmaceutical composition according to claim 14, which is used in combination with a therapeutic drug for hyperlipidemia. 16. The pharmaceutical composition according to claim 15, wherein the therapeutic drug for hyperlipidemia is a statin drug. 17. The statin drug is lovastatin,
The pharmaceutical composition according to claim 16, which is selected from the group consisting of simvastatin, pravastatin, fluvastatin, atorvastatin and cerivastatin. 18. An insulin preparation, a sulfonylurea drug,
Antidiabetic drug selected from the group consisting of insulin secretagogue, sulfonamide drug, biguanide drug, α-glucosidase inhibitor and insulin sensitizer and HLGPa
A pharmaceutical composition for treating or preventing diabetes, which is combined with an inhibitor. 19. The antidiabetic agent is insulin, glibenclamide, tolbutamide, gliclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybsol, metformin hydrochloride,
The pharmaceutical composition for treating or preventing diabetes according to claim 18, which is selected from the group consisting of buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride. 20. The HLGPa inhibitor according to any one of claims 1 to 11.
20. The therapeutic agent for diabetes according to claim 18 or 19, which is the indole compound according to any one of claims 1 to 3, a pharmaceutically acceptable salt or prodrug thereof.